Egaten (triclabendazole): Uses, Dosage, Side Effects & Warnings

Uses

1 INDICATIONS AND USAGE EGATEN ® is indicated for the treatment of fascioliasis in patients 6 years of age and older. EGATEN ® tablet is an anthelmintic indicated for the treatment of fascioliasis in patients 6 years of age and older.

Dosage and administration

The recommended dose of EGATEN is 2 doses of 10 mg/kg given 12 hours apart in patients 6 years of age and older. The 250 mg tablets are functionally scored and divisible into two equal halves of 125 mg. If the dosage cannot be adjusted exactly, round the dose upwards. Take EGATEN orally with food. EGATEN 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. The recommended dose of EGATEN is 2 doses of 10 mg/kg given 12 hours apart in patients 6 years of age and older. ( 2 ) Take orally with food. ( 2 ) Swallow tablets whole or divide in half and take with water, or crush and administer with applesauce. ( 2 ) If the dosage cannot be adjusted exactly, round dose upwards. ( 2 )

Dosage forms and strengths

(triclabendazole) tablet: 250 mg pale red, speckled, capsule shaped, biconvex with “EG ⅁Ǝ” debossed on one side and functionally scored on both sides. Tablets : 250 mg, functionally scored. ( 3 )

Contraindications

4 CONTRAINDICATIONS EGATEN is contraindicated in patients with known hypersensitivity to triclabendazole and/or to other benzimidazole derivatives or to any of the excipients in EGATEN. Patients with known hypersensitivity to triclabendazole, other benzimidazole derivatives or any of the excipients in EGATEN. ( 4 )

Warnings and precautions

Prolongation : Prolongs QTc interval. Monitor electrocardiogram (ECG) in patients with a history of QTc prolongation or with electrolyte imbalance like hypokalemia or who are taking medications which prolong the QTc interval, or on CYP1A2 inhibitors, or have hepatic impairment. ( 5.1 ) 5.1 QT Prolongation EGATEN prolongs the QTc interval [see Clinical Pharmacology (12.2)] . The magnitude of QTc prolongation can increase with increasing treatment duration of EGATEN. Administration of EGATEN concurrently with CYP1A2 inhibitors and use in patients with hepatic impairment may result in increased exposures of triclabendazole and/or its metabolites, and, therefore, may increase the risk for QT prolongation. Monitor electrocardiogram (ECG) in patients with a history of prolongation of the QTc interval or a history of symptoms compatible with a long QT interval or with electrolyte imbalance like hypokalemia, or when EGATEN is used in patients who receive drugs that are known to prolong the QTc interval, or patients taking CYP1A2 inhibitors, or in patients with hepatic impairment. If signs of cardiac arrhythmia occur during treatment with EGATEN, stop the treatment and monitor ECG.

Side effects

Most common adverse reactions (greater than 2%) with triclabendazole 20 mg/kg dose are abdominal pain, hyperhidrosis, nausea, decreased appetite, headache, urticaria, diarrhea, vomiting, musculoskeletal chest pain, and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of triclabendazole was evaluated in 208 adult and pediatric patients 5 years of age and older who participated in 6 clinical trials for the treatment of fascioliasis and received 10 mg/kg or 20 mg/kg of triclabendazole; of these, 6 patients failed the 10 mg/kg dose and were retreated with 20 mg/kg. The 10 mg/kg dosing regimen is not approved [see Dosage and Administration (2)] . In these trials, 186 patients received a single dose of 10 mg/kg and 28 patients received a dose of 20 mg/kg as two divided doses. Pooled data for adverse reactions reported in more than 2% of the patients in these clinical trials for the 10 mg/kg and 20 mg/kg dosing regimens are presented in Table 1. Table 1: Adverse Reactions Occurring in >2% of Patients Who Received a Total of 10 mg/kg or 20 mg/kg Triclabendazole for Fascioliasis Treatment (Pooled Across 6 Studies) 1 Divided doses were given 6-48 hours apart. 2 Abdominal pain upper and abdominal pain. 3 Jaundice and ocular icterus. Adverse Reactions Triclabendazole 10 mg/kg N = 186, n (%) Triclabendazole 20 mg/kg in two divided doses 1 N = 28, n (%) Abdominal pain 2 105 (56) 26 (93) Hyperhidrosis 42 (23) 7 (25) Vertigo 16 (9) 0 Nausea 15 (8) 5 (18) Urticaria 12 (7) 3 (11) Vomiting 11 (6) 2 (7) Headache 11 (6) 4 (14) Dyspnea 9 (5) 0 Pruritus 8 (4) 1 (4) Asthenia 7 (4) 0 Musculoskeletal chest pain 7 (4) 1 (4) Cough 7 (4) 0 Decreased appetite 6 (3) 5 (18) Chest pain 6 (3) 0 Pyrexia 4 (2) 0 Jaundice 3 4 (2) 0 Chest discomfort 4 (2) 0 Diarrhea 0 2 (7) Adverse reactions reported in less than or equal to 2% of patients who received a total of 10 mg/kg of triclabendazole were constipation, biliary colic, arthralgia, back pain, spinal pain, and chromaturia. Some adverse reactions associated with triclabendazole treatment in fascioliasis, e.g., abdominal pain, biliary colic, and jaundice, could be secondary to the infection and may be more frequent and/or severe in patients with a heavy worm burden. The safety profile of triclabendazole 20 mg/kg in divided doses in a non-hepatic parasitic infection (N = 104) was generally similar to the safety profile in fascioliasis, except for a lower incidence of post-treatment abdominal pain. Liver Enzyme Elevations In clinical studies, up to one third of patients had liver enzyme elevations at baseline, which generally improved post-treatment. Of those with normal liver enzyme values at baseline, 6.8%, 4.5%, 4.2% and 3% of patients had post-treatment elevations in bilirubin, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT), respectively. Transient increases in liver enzymes and total bilirubin in fascioliasis patients receiving triclabendazole are reported in the literature. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-marketing use of EGATEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Resistance to triclabendazole has been reported [see Microbiology (12.4)] .

Drug interactions

7 DRUG INTERACTIONS CYP2C19 Substrates : Re-check the plasma concentration of concomitantly administered CYP2C19 substrates after cessation of EGATEN therapy, if the plasma concentrations of the CYP2C19 substrates are elevated during administration of EGATEN. ( 7.1 ) 7.1 Effect of EGATEN on CYP2C19 Substrates No specific clinical drug interaction studies have been conducted for triclabendazole. However, in vitro data suggest the potential for increased plasma concentrations of CYP2C19 substrates with concomitant use of triclabendazole [see Clinical Pharmacology (12.3)] . The potential elevation in concentrations of concomitantly used CYP2C19 substrates is expected to be transient based on the short elimination half-life and short treatment duration of triclabendazole. For those CYP2C19 substrate drugs that require therapeutic monitoring of systemic drug exposures, if the plasma concentrations of the CYP2C19 substrates are elevated during administration of triclabendazole, re-check the plasma concentration of the CYP2C19 substrates after cessation of triclabendazole therapy.

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 birth defects, 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 at doses approximately 0.3 to 1.6 times the maximum recommended human dose (MRHD) of 20 mg/kg based on body 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. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies 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 200 mg/kg/day and 20 mg/kg/day, respectively (approximately 1.6 times and 0.3 times the MRHD based on body surface area comparison, respectively). The animals were treated orally during organogenesis, starting on Day 6 of the pregnancy until Day 15 in rats and Day 18 in rabbits. Maternal toxicity was noted at doses greater than or equal to 100 mg/kg/day in rats and 10 mg/kg/day in rabbits, which was associated with lower fetus weights and delayed ossification. These findings were considered indicative of delayed physiological growth that was secondary to maternal toxicity. No increase in malformation or other abnormalities was observed at any dose level in either species. 8.2 Lactation Risk Summary There are no data on the presence of triclabendazole in human milk, the effects on the breastfed infant, or the effects on milk production. Published animal data indicate that triclabendazole is detected in goat milk when administered as a single dose to one lactating animal. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EGATEN and any potential adverse effects on the breastfed infant from EGATEN or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of EGATEN has been established in pediatric patients aged 6 years and older. Safety and effectiveness of EGATEN in pediatric patients below the age of 6 years have not been established. 8.5 Geriatric Use Clinical studies of EGATEN did not include sufficient numbers of patients aged 65 and over to determine whether the elderly respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. 8.6 Renal Impairment EGATEN has not been studied in patients with renal impairment. 8.7 Hepatic Impairment EGATEN has not been studied in patients with hepatic impairment.

Pregnancy

8.1 Pregnancy Risk Summary There are no available data on EGATEN use in pregnant women to inform a drug-associated risk of major birth defects, 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 at doses approximately 0.3 to 1.6 times the maximum recommended human dose (MRHD) of 20 mg/kg based on body 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. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies 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 200 mg/kg/day and 20 mg/kg/day, respectively (approximately 1.6 times and 0.3 times the MRHD based on body surface area comparison, respectively). The animals were treated orally during organogenesis, starting on Day 6 of the pregnancy until Day 15 in rats and Day 18 in rabbits. Maternal toxicity was noted at doses greater than or equal to 100 mg/kg/day in rats and 10 mg/kg/day in rabbits, which was associated with lower fetus weights and delayed ossification. These findings were considered indicative of delayed physiological growth that was secondary to maternal toxicity. No increase in malformation or other abnormalities was observed at any dose level in either species.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of EGATEN has been established in pediatric patients aged 6 years and older. Safety and effectiveness of EGATEN in pediatric patients below the age of 6 years have not been established.

Geriatric use

8.5 Geriatric Use Clinical studies of EGATEN did not include sufficient numbers of patients aged 65 and over to determine whether the elderly respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Overdosage

The reported symptom of overdosage following ingestion of approximately 54 mg/kg of EGATEN (approximately 2.7 times the recommended dose) was nausea. The patient recovered following osmotic diuresis. In the event of overdose, monitor ECG and institute symptomatic treatment.

Description

(triclabendazole) tablet is an orally administered anthelmintic for immediate release. Triclabendazole is designated chemically as benzimidazole derivative, 6-chloro-5-(2, 3-dichlorophenoxy)-2-(methylthio)-1H-benzimidazole (triclabendazole). The molecular formula for triclabendazole is C 14 H 9 Cl 3 N 2 OS and the molecular weight is 359.65 g/mol. The chemical structure of triclabendazole is shown below: Triclabendazole is a white or almost white, crystalline powder. EGATEN tablets are pale red, speckled, capsule shaped, biconvex tablets, with “EG ⅁Ǝ” debossed on one side and functionally scored on both sides. Each tablet contains 250 mg of triclabendazole. Inactive Ingredients: colloidal silicon dioxide, iron oxide red, lactose monohydrate, maize starch, magnesium stearate, methylhydroxyethylcellulose. The chemical structure of triclabendazole is a white or almost white, crystalline powder.

Mechanism of action

12.1 Mechanism of Action Triclabendazole is an anthelmintic against Fasciola species [see Microbiology (12.4)] .

How supplied

How Supplied EGATEN (triclabendazole) tablets are supplied as pale red, speckled, capsule shaped, biconvex tablets with “EG ⅁Ǝ” debossed 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).

Patient 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 with electrolyte imbalance like hypokalemia or when EGATEN is used in patients who receive drugs that are known to prolong the QTc interval or on CYP1A2 inhibitors or have hepatic impairment 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 T2022-10

Active ingredients

Triclabendazole in 1 product

Egaten NDC products (1)

NDC	Strength & form	Labeler	Type
0078-0937	Triclabendazole 250 mg/1 Tablet	Novartis Pharmaceuticals Corporation	NDA

Frequently asked questions

What is Egaten used for?

1 INDICATIONS AND USAGE EGATEN ® is indicated for the treatment of fascioliasis in patients 6 years of age and older. EGATEN ® tablet is an anthelmintic indicated for the treatment of fascioliasis in patients 6 years of age and older.

What are the side effects of Egaten?

Most common adverse reactions (greater than 2%) with triclabendazole 20 mg/kg dose are abdominal pain, hyperhidrosis, nausea, decreased appetite, headache, urticaria, diarrhea, vomiting, musculoskeletal chest pain, and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1… See the full label for the complete list.

Who makes Egaten?

Egaten is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.