Triclabendazole

BRAND NAMES

Egaten: A well-known brand name for human and veterinary use.

Fasinex: Another brand name for triclabendazole.

Triclafas: A brand name available in different formulations.

Other Veterinary Brands:

Tribex

Triclaben

Triclacert

Triclafas Drench

Specific Product Names:

Triclab 250 Mg Tablet

Triclabend 250 (Triclabendazole Tablets 250 Mg)

MECHANISM OF ACTION

Triclabendazole acts by disrupting vital cellular processes in liver flukes, leading to their death. Its mechanism of action primarily involves interference with the parasite’s microtubule formation. The drug binds to β-tubulin, a key structural protein in the cytoskeleton of the parasite, preventing the polymerization of microtubules. This disruption affects essential functions such as motility, nutrient uptake, secretion, and reproductive activity.

Additionally, triclabendazole and its active metabolite, sulfoxide, cause significant alterations in the tegument (outer surface) of the fluke, leading to vacuolization, disruption of the membrane, and eventual detachment from host tissues. These combined effects result in paralysis, metabolic dysfunction, and death of both immature and adult Fasciola species. In summary, triclabendazole kills liver flukes by binding to β-tubulin, disrupting microtubule formation, damaging the tegument, and impairing essential metabolic functions.

PHARMACOKINETICS

Absorption

Triclabendazole is quickly absorbed after oral administration and is converted into its active metabolites, sulfoxide and sulfone. Its absorption is greatly improved when taken with a fatty meal, resulting in higher blood concentrations of these active forms and enhanced effectiveness against the parasites.

Distribution

Although the volume of distribution (V_{d})) for the parent compound triclabendazole has not been reported, its active metabolite, triclabendazole sulfoxide, has an estimated apparent (V_{d}) of about 1 L/kg in humans. This value is considered approximate, as the (V_{d}) can vary depending on several important pharmacokinetic factors.

Metabolism

Triclabendazole undergoes metabolism to form its active sulfoxide metabolite, which is subsequently oxidized to the active sulfone metabolite. These metabolites are primarily eliminated through the biliary tract and excreted in the feces, while a smaller amount is excreted in the urine. The plasma half-lives of triclabendazole and its sulfoxide and sulfone metabolites are approximately 8, 14, and 11 hours, respectively.

Excretion

Triclabendazole and its metabolites are mainly excreted via the biliary route into the feces, which accounts for the majority of the drug’s elimination. A smaller proportion is excreted in the urine. After oral administration, most of the administered dose is recovered from feces as the sulfoxide and sulfone metabolites, indicating extensive metabolism before excretion. This biliary-fecal excretion pathway reflects triclabendazole’s lipophilic nature and its extensive hepatic metabolism.

PHARMACODYNAMICS

The pharmacodynamic activity of triclabendazole is mainly attributed to its active metabolite, triclabendazole sulfoxide, which is more potent than the parent compound. Although the precise mechanism is not fully understood, it is thought to involve disruption of microtubule-dependent processes or inhibition of adenylate cyclase in the parasite. These actions impair the parasite’s motility and vital functions, ultimately resulting in its death.

ADMINISTRATION

Triclabendazole is administered orally, usually in the form of tablets. It should be taken with food, preferably a fatty meal, to enhance absorption and increase plasma concentrations of its active metabolites. The standard dosing regimen for human fascioliasis is a single oral dose of 10 mg/kg, which may be repeated after 12–24 hours if needed, depending on the severity of infection and clinical response. The tablets can be swallowed whole or, if necessary, crushed and mixed with food for easier administration. In veterinary use, dosing and schedules vary by animal species and parasite burden.

DOSAGE AND STRENGTH

• Dosage for humans (fascioliasis):

Single dose: 10 mg/kg orally

Alternative regimen: In some cases, a second 10 mg/kg dose may be given 12–24 hours later if required.

• Tablet strength:

Commonly available as 250 mg tablets.

• Administration tips:

Should be taken with food, preferably a fatty meal, to enhance absorption and increase effectiveness.

• Veterinary use:

Dosage varies depending on the species, weight, and severity of infection.

FOOD INTERACTIONS

Triclabendazole’s absorption is significantly enhanced when taken with a fatty meal, which increases the plasma concentration of its active metabolite, triclabendazole sulfoxide, and improves its effectiveness against parasites. There are no specific foods that need to be avoided, but taking the drug on an empty stomach may reduce its absorption and efficacy. Therefore, it is recommended to administer triclabendazole with food, preferably containing some fat, to ensure optimal therapeutic effect.

DRUG INTERACTIONS

Triclabendazole has a relatively low potential for drug interactions. It is metabolized in the liver primarily through cytochrome P450 enzymes, so co-administration with strong CYP450 inducers or inhibitors may alter its metabolism and affect efficacy or toxicity. Caution is also advised when using triclabendazole with other hepatotoxic drugs, as this may increase the risk of liver-related side effects. Apart from the absorption-enhancing effect of fatty meals, no significant interactions with other medications have been reported.

CONTRAINDICATIONS

Triclabendazole is contraindicated in individuals with a known hypersensitivity to the drug or other benzimidazole derivatives. It should be used with caution during pregnancy, especially in the first trimester, and only if the potential benefits outweigh the risks. The drug is also not recommended for patients with severe liver impairment due to its extensive hepatic metabolism. Additionally, safety and efficacy may not be established in very young children, so dosing in this group should follow local guidelines and clinical judgment.

SIDE EFFECTS

Common side effects

• Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea, and decreased appetite.

• Neurological: Headache, dizziness, or lightheadedness.

• Other: Fever, increased sweating, skin rash, or hives. 

Less common side effects

Some patients may experience less frequent but notable side effects, such as: 

• Musculoskeletal: Joint pain, back pain, or muscle pain and stiffness.

• Respiratory: Cough, chest pain or tightness, or difficulty breathing.

• Urinary: Abnormal color of urine. 

OVERDOSE

• Severe nausea and vomiting.

• Abdominal pain.

• Dizziness or lightheadedness.

• Unusual or heavy sweating.

• Abnormal heart rhythm.

• Allergic reaction.

• Liver issues.

• Visual impairment.

TOXICITY

Triclabendazole is generally well tolerated, and serious toxicity is rare. Adverse effects are usually mild and transient, including abdominal pain, nausea, vomiting, headache, dizziness, and fatigue. Some patients may experience elevated liver enzymes due to its hepatic metabolism, but significant hepatotoxicity is uncommon. In rare cases, hypersensitivity reactions such as rash, itching, or fever may occur. Overdose reports are limited, but symptoms may include gastrointestinal disturbances and liver enzyme elevation. Supportive care is usually sufficient, as triclabendazole has a wide therapeutic index.