Triclabendazole (Systemic)


VA CLASSIFICATION
Primary: AP200

Commonly used brand name(s): Fasinex.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Anthelmintic (systemic)—

Indications

Note: Because triclabendazole is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this medication in these countries.

General considerations
Triclabendazole is a benzimidazole compound used routinely since 1983 in veterinary practice for the treatment of fascioliasis. It was not used in humans until the 1989 epidemic of fascioliasis near the Caspian Sea when Iranian authorities approved the use of the veterinary formulation to treat the infection. {01} {02} (Fascioliasis normally is a disease of domestic herbivorous animals such as sheep, cattle, and goats, which are the normal hosts. Humans are accidental hosts; infection results from eating uncooked, and usually unwashed, aquatic vegetables [e.g., watercress] contaminated with encysted parasitic larvae. Fascioliasis is endemic in 61 countries and has become a foodborne infection of public importance in areas of the world such as the Andean highlands of Bolivia, Ecuador, and Peru, the Nile delta of Egypt, and northern Iran. It is estimated that 2.4 million people are infected worldwide and more than 180 million are at risk of infection.) {01}

Triclabendazole has shown no activity against nematodes. It differs from the other benzimidazole anthelmintics (e.g., albendazole, mebendazole) currently used in humans since these compounds have selective activity against nematodes and have no significant activity against flukes and other trematode helminths. {01} {02}

Accepted

[Fascioliasis (treatment)]1—Triclabendazole is used as a primary agent in the treatment of fascioliasis caused by Fasciola hepatica (sheep liver fluke) and Fasciola gigantica (giant liver fluke). {01} {02} {07} {08} {11} {13}

[Paragonimiasis (treatment)]1—Triclabendazole is used as an alternative agent in the treatment of paragonimiasis caused by Paragonimus westermani (lung fluke) {01} {02} {13} {16}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Related to the benzimidazole-2–carbamate anthelmintics {03} {04}.
Molecular weight—
    359.66 {17}

Mechanism of action/Effect:

Fasciolicidal not only against the adult worms present in the biliary ducts, but also against the immature larval stages of Fasciola migrating through the hepatic parenchyma; the mechanism of action is not thoroughly understood; however, triclabendazole is shown to penetrate into liver flukes by transtegumentary absorption followed by inhibition of the parasite's motility, probably related to the destruction of the microtubular structure, resulting in the death of the parasite; the immobilizing effect is paralleled by changes in the parasite's resting tegumental membrane potential, strongly inhibiting the release of proteolytic enzymes, a process that appears critical to the survival of the parasite {05} {06} {07}.

Absorption:

Following oral administration, triclabendazole is absorbed from the gastrointestinal tract; absorption is increased twofold to threefold when triclabendazole is taken after a fatty meal {02} {08}.

Distribution:

Triclabendazole and its metabolites attain high concentrations in the biliary tract, through which they are excreted back into the intestine over a period of several days {02}; less than 1% of orally administered triclabendazole is distributed into breast milk {09}.

Biotransformation:

Triclabendazole is oxidized to sulfoxide (the primary metabolite) and sulfone (present in lesser amounts) over the first 24 hours following oral administration {02}.

Time to peak concentration:

Approximately 8 hours {02}.

Elimination:
    Fecal—Approximately 95% of orally administered triclabendazole (unchanged or as the primary metabolite) is excreted in the feces {09}.
    Renal—Approximately 2% is excreted in the urine {09}.


Precautions to Consider

Mutagenicity

Studies conducted in laboratory animals have not shown triclabendazole to be mutagenic {07} {08} {09} {15}.

Pregnancy/Reproduction

Pregnancy—
Studies in humans have not been done.

Studies in animals have not shown that triclabendazole causes adverse effects in the fetus. {02} {07} {09} {10}

Breast-feeding

Triclabendazole is distributed into breast milk {09}.

Pediatrics

Appropriate studies on the relationship of age to the effects of triclabendazole have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date. {02} {08}


Geriatrics


Appropriate studies on the relationship of age to the effects of triclabendazole have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date. {02} {08}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For liver and lung flukes
» Stool examinations    (routine stool examinations and concentration methods, preferably the cup sedimentation with tap water technique [which has a higher detection sensitivity than the Teleman's technique], may be required prior to treatment of fascioliasis to detect the presence of eggs and approximately 3 months following treatment with triclabendazole, along with clinical assessment of the patient, to determine efficacy of medication or establish proof of cure; absence of Fasciola eggs in stool of some patients is probably due to the fact that these patients harbor parasites that are immature and in the early stage of migration {08} {11} {18} {19})

    (routine stool examinations also may be required prior to treatment of paragonimiasis to detect the presence of eggs for definitive diagnosis)


» Serological tests    (complement fixation [CF] test or, preferably, enzyme-link immunosorbent assay [ELISA], which has a high sensitivity in detecting chronic human fascioliasis, may be performed prior to treatment and approximately 6 and 12 months following treatment to monitor therapeutic response {08})

    (passive hemagglutination assay or ELISA may be performed prior to treatment and approximately 6 and 12 months following treatment of paragonimiasis to monitor therapeutic response {16})


For liver flukes
» Duodenal bile aspiration    (when routine stool examinations are negative for the organism, duodenal bile aspiration may be performed to detect the presence of the parasites in the bile aspirates; this procedure may be done prior to and following treatment with triclabendazole {03} {08})


For lung flukes
» Sputum examinations    (routine examination of the sputum may be required prior to treatment to detect the presence of eggs and approximately 3 or 12 months following treatment with triclabendazole, along with clinical assessment of the patient, to determine efficacy of medication or establish proof of cure {02} {16})


Chest roentgenogram     (chest roentgenogram may be performed prior to and following treatment to determine therapeutic response as shown by a reduction in the number of nodular opacities {02})




Side/Adverse Effects

Note: Treatment with triclabendazole generally is well-tolerated. Except for the transient and self-limiting biliary obstruction caused by the dying liver flukes (similar to the complication reported during the natural course of the disease unaffected by chemotherapy {07} {14}) in the treatment of fascioliasis, use of triclabendazole has not been associated with serious adverse events. {01} {02} {07} {08}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence rare
    
Gastrointestinal disturbances {02}{19}(abdominal cramps; diarrhea)

Note: Transient diarrhea was reported by a small minority of patients receiving triclabendazole at a high dose [20 mg per kg of body weight in divided doses] for the treatment of paragonimiasis. {02} {19}






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Triclabendazole (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to triclabendazole





Breast-feeding—Triclabendazole is distributed into breast milk

Proper use of this medication
» Taking with food containing fat to increase absorption

» Compliance with full course of therapy; second course may be required to clear up the infection completely

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Importance of physician checking progress after treatment

Checking with physician if no improvement after completing course of therapy


General Dosing Information
Triclabendazole should be taken after a meal, preferably a fatty one, because this significantly increases the absorption of triclabendazole {01} {02} {12}.


Oral Dosage Forms

Note: Because triclabendazole is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this medication in these countries.

TRICLABENDAZOLE TABLETS

Usual adult and adolescent dose
[Fascioliasis]1
Oral, 10 mg per kg of body weight as a single dose {01} {02} {08} {11} {13}. Treatment may be repeated after two weeks {11} or after six months {08} if necessary. The World Health Organization (WHO) recommends 20 mg per kg of body weight given twelve hours apart for one day for severe cases of fascioliasis {01}.

[Paragonimiasis]1
Oral, 5 mg per kg of body weight once a day for three days {13} or 10 mg per kg of body weight as a single dose {16}. WHO recommends 20 mg per kg of body weight given in two divided doses for one day {02} {13}.


Usual adult and adolescent prescribing limits
A total cumulative dose of 38 mg per kg of body weight given to a non-infected human volunteer resulted in good clinical and laboratory toleration of triclabendazole {07}.

Usual pediatric dose
[Fascioliasis]1
Dosage has not been established. However, 10 mg per kg of body weight given orally as a single dose has been used. {02} {08}

[Paragonimiasis]1
Dosage has not been established. However, 10 mg per kg of body weight given orally as a single dose has been used {16}. WHO recommends 20 mg per kg of body weight given orally in two divided doses in one day.


Usual pediatric prescribing limits
20 mg per kg of body weight {02}.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—
Not commercially available.

Egypt—


250 mg [Fasinex{03}{07}{13} (scored){01}]

Packaging and storage:
Store below 40 ºC (104 ºF), preferably between 15 and 30 ºC (59 and 86 ºF), in a well-closed container, unless otherwise specified by manufacturer.



Developed: 12/29/1998



References
  1. World Health Organization. Triclabendazole and fascioliasis—a new drug to combat an age-old disease. Geneva: World Health Organization Press Office; 1998. Fact Sheet No. 191.
  1. Triclabendazole and trematode worm infections. Drugs Quarterly 1997; 1(1): 38-9.
  1. Abdul-Hadi S, Contreras R, Tombazzi C, et al. Hepatic fascioliasis: case report and review. Rev Inst Med Trop Sao Paulo 1996; 38(1): 69-73.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 31st ed. London: The Pharmaceutical Press; 1996. p. 127.
  1. Coles GC. Anthelmintic activity of triclabendazole. J Helminthol 1986; 60(3): 210-2.
  1. Bennett JL, Kohler P. Fasciola hepatica: action in vitro of triclabendazole on immature and adult stages. Exp Parasitol 1987; 63(1): 49-57.
  1. Wessely K, Reischig HL, Heinerman M, et al. Human fascioliasis treated with triclabendazole (Fasinex) for the first time. Trans R Soc Trop Med Hyg 1988; 82: 743-5.
  1. Apt W, Aguilera X, Vega F, et al. Treatment of human chronic fascioliasis with triclabendazole: drug efficacy and serologic response. Am J Trop Med Hyg 1995; 532-5.
  1. Faria SLS. Control quimioterapeutico contra Fasciola hepatica en bovinos, en una zona endemica con infestacion todo el ano. Guanare, Universidad Nacional Experimental de Los Llanos Occidentales Ezequiel Zamora UNELLEZ; 1994. p. 1-107.
  1. Yoshimura H. Teratogenic evaluation of triclabendazole in rats. Toxicology 1987; 43: 283-7.
  1. Hammouda NA, El-Mansoury ST, El-Azzouni MZ, et al. Therapeutic effect of triclabendazole in patients with fascioliasis in Egypt: a preliminary study. J Egypt Soc Parasitol 1995; 25(1): 137-43.
  1. Loutan L, Bouvier M, Rojanawisut B, et al. Single treatment of invasive fascioliasis with triclabendazole. Lancet 1989; 2: 383.
  1. Abramowicz M, editor. Drugs for parasitic infections. Med Lett Drugs Ther 1998; 40(1017): 17-26.
  1. Belgraier AH. Common bile duct obstruction due to Fasciola hepatica. N Y State J Med 1976; 76: 936-7.
  1. Robinson CP. Triclabendazole. Drugs of Today 1985; 21: 227-33.
  1. Ripert C, Couprie B, Moyou R, et al. Therapeutic effect of triclabendazole in patients with paragonimiasis in Cameroon. A pilot study. Trans R Soc Trop Med Hyg 1992; 86: 417.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 755.
  1. Panel comment, 10/98.
  1. Panel comment, 10/98.
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