Identification
- Summary
Triclabendazole is an anthelmintic drug used to treat fascioliasis.
- Brand Names
- Egaten
- Generic Name
- Triclabendazole
- DrugBank Accession Number
- DB12245
- Background
Triclabendazole, manufactured by Novartis pharmaceuticals, is an antihelminthic drug that was approved by the FDA in February 2019 for the treatment of fascioliasis in humans.Label,4 Fascioliasis is a parasitic infection often caused by the helminth, Fasciola hepatica, which is also known as “the common liver fluke” or “the sheep liver fluke” or by Fasciola gigantica, another helminth. These parasites can infect humans following ingestion of larvae in contaminated water or food.
Triclabendazole was previously used in the treatment of fascioliasis in livestock, but is now approved for human use. This drug is currently the only FDA-approved drug for individuals with fascioliasis, which affects 2.4 million people worldwide.2,4
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Triclabendazole (DB12245)
- Weight
- Average: 359.65
Monoisotopic: 357.9501172 - Chemical Formula
- C14H9Cl3N2OS
- Synonyms
- Triclabendazole
- External IDs
- EGA230B
- NVP-EGA230
Pharmacology
- Indication
This drug is indicated for the treatment of fascioliasis in patients aged 6 years old and above.Label,4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Fascioliasis •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Triclabendazole and its metabolites are active against both the immature and mature worms of Fasciola hepatica and Fasciola gigantica helminths.Label
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.Label
- Mechanism of action
Triclabendazole is an anthelmintic agent against Fasciola species.Label
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.Label
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.Label
Target Actions Organism UExcretory Secretory (ES) proteins inhibitorFasciola hepatica - Absorption
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.Label
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.Label
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 Label.
- Volume of distribution
The apparent volume of distribution (Vd) of the sulfoxide metabolite in fed patients is about 1 L/kg.Label
- Protein binding
Protein-binding of triclabendazole, sulfoxide metabolite and sulfone metabolite in human plasma was 96.7%, 98.4% and 98.8% respectively.Label
- Metabolism
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.Label
Hover over products below to view reaction partners
- Route of elimination
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.Label
- Half-life
The plasma elimination half-life (t1/2) of triclabendazole, the sulfoxide and sulfone metabolites in human is about 8, 14, and 11 hours, respectively.Label
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Oral LD50 (rat): >8 gm/kg; Oral LD50 (mouse): >8 gm/kgMSDS
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.Label
Carcinogenesis/Mutagenesis
No genotoxic risk was noted for triclabendazole tested in 6 genotoxicity in vitro and in vivo assays.Label
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.Label
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.Label
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Triclabendazole can be increased when it is combined with Abametapir. Abatacept The metabolism of Triclabendazole can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Triclabendazole. Abiraterone The serum concentration of Triclabendazole can be increased when it is combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Triclabendazole. - Food Interactions
- Take with food. Taking triclabendazole with food increases the bioavailability of triclabendazole and its sulfoxide metabolite.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Fasinex
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Egaten Tablet 250 mg/1 Oral Novartis Pharmaceuticals Corporation 2019-02-13 Not applicable US 
Categories
- ATC Codes
- P02BX04 — Triclabendazole
- Drug Categories
- Anthelmintics
- Anti-Infective Agents
- Antihelminthic
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiplatyhelmintic Agents
- Antitrematodals
- Benzimidazoles
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2A6 Inhibitors
- Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Cytochrome P450 2A6 Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Ethers
- Direct Parent
- Diarylethers
- Alternative Parents
- Benzimidazoles / Phenoxy compounds / Phenol ethers / Dichlorobenzenes / Alkylarylthioethers / Aryl chlorides / Imidazoles / Heteroaromatic compounds / Sulfenyl compounds / Azacyclic compounds show 4 more
- Substituents
- 1,2-dichlorobenzene / Alkylarylthioether / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Aryl thioether / Azacycle / Azole / Benzenoid / Benzimidazole show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 4784C8E03O
- CAS number
- 68786-66-3
- InChI Key
- NQPDXQQQCQDHHW-UHFFFAOYSA-N
- InChI
- InChI=1S/C14H9Cl3N2OS/c1-21-14-18-9-5-8(16)12(6-10(9)19-14)20-11-4-2-3-7(15)13(11)17/h2-6H,1H3,(H,18,19)
- IUPAC Name
- 6-chloro-5-(2,3-dichlorophenoxy)-2-(methylsulfanyl)-1H-1,3-benzodiazole
- SMILES
- CSC1=NC2=C(N1)C=C(Cl)C(OC1=CC=CC(Cl)=C1Cl)=C2
References
- General References
- El-Tantawy WH, Salem HF, Mohammed Safwat NA: Effect of Fascioliasis on the pharmacokinetic parameters of triclabendazole in human subjects. Pharm World Sci. 2007 Jun;29(3):190-8. doi: 10.1007/s11096-006-9069-8. Epub 2007 Jan 30. [Article]
- Manouchehri Naeini K, Mohammad Nasiri F, Rokni MB, Kheiri S: Seroprevalence of Human Fascioliasis in Chaharmahal and Bakhtiyari Province, Southwestern Iran. Iran J Public Health. 2016 Jun;45(6):774-80. [Article]
- FDA Approves EGATEN (Triclabendazole) for Fascioliasis in Patients 6 Years of Age or Older [Link]
- Novartis receives FDA approval for Egaten® for the treatment of fascioliasis, a neglected tropical disease [Link]
- FDA Approved Drug Products: EGATEN (triclabendazole) tablets [Link]
- External Links
- KEGG Drug
- D07364
- PubChem Compound
- 50248
- PubChem Substance
- 347828523
- ChemSpider
- 45565
- BindingDB
- 58491
- 2118525
- ChEBI
- 94759
- ChEMBL
- CHEMBL1086440
- ZINC
- ZINC000001444556
- PDBe Ligand
- JA9
- Wikipedia
- Triclabendazole
- PDB Entries
- 7eri
- FDA label
- Download (251 KB)
- MSDS
- Download (26.1 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Fascioliasis 1 Not Available No Longer Available Not Available Parasitic Diseases 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 250 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 189-191 https://www.trc-canada.com/product-detail/?T773825 boiling point (°C) 496 http://sitem.herts.ac.uk/aeru/vsdb/Reports/1773.htm water solubility 1.0 mg/dL http://sitem.herts.ac.uk/aeru/vsdb/Reports/1773.htm logP 3.48 http://helminto.inta.gob.ar/Fasciola/Alvarezetal.pdf - Predicted Properties
Property Value Source Water Solubility 0.000508 mg/mL ALOGPS logP 5.5 ALOGPS logP 5.88 Chemaxon logS -5.8 ALOGPS pKa (Strongest Acidic) 10.46 Chemaxon pKa (Strongest Basic) 4.54 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 37.91 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 87.86 m3·mol-1 Chemaxon Polarizability 34.02 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 168.90404 predictedDeepCCS 1.0 (2019) [M+H]+ 171.26202 predictedDeepCCS 1.0 (2019) [M+Na]+ 177.35518 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein group
- Organism
- Fasciola hepatica
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- This is a possible target of this drug, but has not been confirmed.
- General Function
- Not Available
- Specific Function
- Protein domain specific binding
Components:
References
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Giri P, Gupta L, Naidu S, Joshi V, Patel N, Giri S, Srinivas NR: In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone. Drug Metab Lett. 2018;12(2):101-116. doi: 10.2174/1872312812666180816164626. [Article]
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Giri P, Gupta L, Naidu S, Joshi V, Patel N, Giri S, Srinivas NR: In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone. Drug Metab Lett. 2018;12(2):101-116. doi: 10.2174/1872312812666180816164626. [Article]
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Giri P, Gupta L, Naidu S, Joshi V, Patel N, Giri S, Srinivas NR: In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone. Drug Metab Lett. 2018;12(2):101-116. doi: 10.2174/1872312812666180816164626. [Article]
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Giri P, Gupta L, Naidu S, Joshi V, Patel N, Giri S, Srinivas NR: In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone. Drug Metab Lett. 2018;12(2):101-116. doi: 10.2174/1872312812666180816164626. [Article]
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56501.005 Da
References
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Giri P, Gupta L, Naidu S, Joshi V, Patel N, Giri S, Srinivas NR: In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone. Drug Metab Lett. 2018;12(2):101-116. doi: 10.2174/1872312812666180816164626. [Article]
- Egaten FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Egaten FDA label [File]
Drug created at October 20, 2016 21:42 / Updated at August 19, 2021 10:28