156 Profile inal pain are common during treatment with tiabenda- Tetramisole hydrochloride is an used in veterinary S S S S zole. Other adverse effects occurring occasionally in- Santoniini; Santonina; Santoninum. (3 ,3a ,5a ,9b )-3a,5,5a,9b- medicine for the control of infections. It is a racemic Tetrahydro-3,5a,9-trimethylnaphtho[1,2-b]furan-2,8(3H,4H)-di- mixture and the laevo-isomer, hydrochloride (p.147), clude pruritus, skin rashes, headache, fatigue, one. accounts for most of its activity. drowsiness, drying of mucous membranes, hypergly- Сантонин Preparations caemia, disturbance of vision including colour vision, C15H18O3 = 246.3. Proprietary Preparations (details are given in Part 3) leucopenia, tinnitus, effects on the liver including CAS — 481-06-1. Braz.: Ascarizole†; Tetramizotil†. cholestasis and parenchymal damage (in some cases Multi-ingredient: India: Jetomisol-P. severe and irreversible), enuresis, crystalluria, and CH bradycardia and hypotension. There have also been re- 3 ports of erythema multiforme, fatal Stevens-Johnson Thiacetarsamide (rINNM) syndrome, toxic epidermal necrolysis, convulsions, Thiacétarsamide; Thiacetarsamidum; Tiacetarsamida. p-[Bis(car- and effects on mental state. CH3 O boxymethylmercapto)arsino]benzamide; 4-Carbamylphenyl Fever, chills, angioedema, and lymphadenopathy have bis[carboxymethylthio]arsenite. CH3 O been reported, but may represent allergic response to Тиацетарсамид dead parasites rather than to tiabendazole. O C11H12AsNO5S2 = 377.3. CAS — 531-72-6. The urine of some patients taking tiabendazole may Pharmacopoeias. In Jpn. ATC Vet — QP52AX08. have a characteristic odour similar to that after eating Profile asparagus; it is attributed to the presence of a tiabenda- zole metabolite. Santonin is a crystalline lactone obtained from the dried unex- O panded flowerheads of Artemisia cina (santonica, wormwood) Effects on the salivary glands. Dry mouth with swollen pa- OH and other species of Artemisia (Compositae). It was formerly rotid and salivary glands suggestive of the sicca complex preced- used as an anthelmintic in the treatment of roundworm (Ascaris) ed the development of cholestatic jaundice in a 17-year-old boy infection, but has been superseded by other less toxic an- 1 H N S given tiabendazole. thelmintics. 2 1. Davidson RN, et al. Intrahepatic cholestasis after thiabendazole. It is used as a flavour in food. As Trans R Soc Trop Med Hyg 1988; 82: 620. O S Hypersensitivity. Severe erythema multiforme developed in a patient 16 days after a course of tiabendazole.1 Many of the le- sions encircled pre-existing melanocytic naevi. (USAN, rINN) OH 1. Humphreys F, Cox NH. Thiabendazole-induced erythema multi- Selamectina; Sélamectine; Selamectinum; Selamektiini; Selamek- forme with lesions around melanocytic naevi. Br J Dermatol tin; UK-124114. (2aE,4E,5′S,6S,6′S,7S,8E,11R,13R,15S,17aR,20aR, O 1988; 118: 855–6. 20bS)-6′-Cyclohexyl-7-[(2,6-dideoxy-3-O-methyl-α-L-arabino- hexopyranosyl)oxy]-3′,4′,5′,6,6′,7,10,11,14,15,20a,20b-dodec- Profile Precautions ahydro-20b-hydroxy-5′,6,8,19-tetramethylspiro(11,15-methano- Thiacetarsamide is an anthelmintic used in veterinary medicine. Tiabendazole should be used with caution in patients 2H,13H,17H-furo[4,3,2-p,q][2,6]benzodioxacyclooctadecin- with hepatic or renal impairment. Tiabendazole causes 13,2′-[2H]pyran)-17,20(17aH)-dione 20-oxime. drowsiness in some patients and those affected should Селамектин Thiophanate (BAN) not drive or operate machinery. Tiofanato. 4,4′-o-Phenylenebis(ethyl 3-thioallophanate). C43H63NO11 = 770.0. Tiabendazole should not be used in mixed worm infec- CAS — 165108-07-6. C14H18N4O4S2 = 370.4. tions involving Ascaris lumbricoides as it can cause ATC Vet — QP54AA05. CAS — 23564-06-9. ATC Vet — QP52AC04. these roundworms to migrate; live roundworms have emerged through the mouth or nose.

CH3 CH3 Pregnancy. Tiabendazole is teratogenic in mice although there O S H3C O O O are no adequate and well controlled studies in human pregnancy. O Renal impairment. Tiabendazole and its 5-hydroxy metabo- 3C OH N NH H H H lite did not accumulate in an anephric patient on haemodialysis HO H3C N N OCH3 and haemoperfusion who was treated for severe strongyloidia- O OO sis.1 However, the potentially toxic conjugated glucuronide and CH3 OH S O sulfate metabolites did accumulate. The clearance of all 3 metab- olites was poor by haemodialysis; haemoperfusion was much more efficient, although for rapid removal the haemoperfusion O Profile columns should be changed every hour. CH3 Thiophanate is an anthelmintic used in veterinary medicine for H 1. Bauer L, et al. The pharmacokinetics of thiabendazole and its N the control of nematode infections. metabolites in an anephric patient undergoing hemodialysis and OH hemoperfusion. J Clin Pharmacol 1982; 22: 276–80. Pharmacopoeias. In Eur. (see p.vii) for veterinary use only. Interactions Ph. Eur. 6.2 (Selamectin for Veterinary Use). A semi-synthetic Tiabendazole (BAN, rINN) product derived from a fermentation product. A white or almost Xanthines. For the effect of tiabendazole on serum concentra- white, hygroscopic powder. Practically insoluble in water; solu- E233; MK-360; Thiabendazole (USAN); Tiabendatsoli; Tiabenda- tions of theophylline, see p.1145. ble in acetone and in dichloromethane; freely soluble in isopro- zol; Tiabendazolas; Tiabendazolum. 2-(Thiazol-4-yl)-1H-benzim- pyl alcohol; sparingly soluble in methyl alcohol. Store in airtight idazole. Pharmacokinetics containers. Тиабендазол Tiabendazole is readily absorbed from the gastrointes- Profile C10H7N3S = 201.2. tinal tract and reaches peak concentrations in the plas- Selamectin is an anthelmintic and ectoparasiticide CAS — 148-79-8. ma after 1 to 2 hours. It is metabolised to 5-hydroxythi- used in veterinary medicine. ATC — D01AC06; P02CA02. abendazole and excreted principally in the urine as ATC Vet — QD01AC06; QP52AC10. glucuronide or sulfate conjugates; about 90% is recov- ered in the urine within 48 hours of ingestion, but only Tetramisole Hydrochloride (BANM, USAN, rINNM) H 5% in the faeces. Absorption may occur from prepara- N Hidrocloruro de tetramisol; ICI-50627; McN-JR-8299-11; R- S tions applied to the skin or eyes. 8299; Tétramisole, Chlorhydrate de; Tetramisoli Hydrochlori- ◊ References. dum. (±)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b] hy- N N 1. Tocco DJ, et al. Absorption, metabolism, and excretion of thia- drochloride. bendazole in man and laboratory animals. Toxicol Appl Pharma- col 1966; 9: 31–9. Тетрамизола Гидрохлорид Pharmacopoeias. In Chin., Eur. (see p.vii), Int., and US. Ph. Eur. 6.2 (Tiabendazole). A white or almost white crystalline C11H12N2S,HCl = 240.8. Uses and Administration CAS — 5036-02-2 (tetramisole); 5086-74-8 (tetramisole powder. Practically insoluble in water; slightly soluble in alcohol hydrochloride). and in dichloromethane; it dissolves in dilute mineral acids. Pro- Tiabendazole, a derivative, is an an- tect from light. thelmintic with activity against most nematode worms; USP 31 (Thiabendazole ). A white to practically white, odour- activity against some larval stages and ova has also H N S less or practically odourless, powder. Practically insoluble in wa- been demonstrated. The mode of action is not certain, ter; slightly soluble in alcohol and in acetone; very slightly solu- ble in chloroform and in ether. but tiabendazole may inhibit the fumarate-reductase N system of worms thereby interfering with their source (tetramisole) Adverse Effects of energy. Dizziness and gastrointestinal disturbances, especially Tiabendazole is used in the treatment of cutaneous lar- Pharmacopoeias. In Fr. for veterinary use only. anorexia, nausea and vomiting, diarrhoea, and abdom- va migrans, dracunculiasis (guinea worm infection), Santonin/ 157 and . It may also be used in the treatment of . Tiabendazole may be used in the treatment of ingly being used in the treatment of human fascioliasis, and is strongyloidiasis, and can provide symptomatic relief strongyloidiasis (p.138), but or are gen- under investigation for the treatment of human paragonimiasis. during the larval invasion stage of trichinosis. Tiaben- erally preferred. References. Liver fluke infections. Although or are dazole is also active against some intestinal , 1. Grove DI. Treatment of strongyloidiasis with thiabendazole: an used to treat fascioliasis (p.137), some consider triclabendazole 1 but should not be used as primary therapy; the treat- analysis of toxicity and effectiveness. Trans R Soc Trop Med Hyg to be the drug of choice. A suggested oral dose is 10 mg/kg, ment of mixed infections including is not 1982; 76: 114–18. given as a single dose after food; the dose may be repeated once.1 2. Barnish G, Barker J. An intervention study using thiabendazole Several studies2-7 have demonstrated the efficacy of triclabenda- recommended since tiabendazole may cause the suspension against strongyloides fuelleborni-like infections in zole in fascioliasis. worms to migrate to other body organs causing serious Papua New Guinea. Trans R Soc Trop Med Hyg 1987; 81: 60–3. 3. Boken DJ, et al. Treatment of Strongyloides stercoralis hyperin- 1. Abramowicz M, ed. Drugs for parasitic infections. 1st ed. New complications. For discussions of the treatment of the fection syndrome with thiabendazole administered per rectum. Rochelle NY: The Medical Letter, 2007. above infections see under Choice of Anthelmintic, Clin Infect Dis 1993; 16: 123–6. 4. Gann PH, et al. A randomized trial of single- and two-dose iver- 2. Apt W, et al. Treatment of human chronic fascioliasis with tricla- p.134, and under the individual headings below. mectin versus thiabendazole for treatment of strongyloidiasis. J bendazole: drug efficacy and serologic response. Am J Trop Med Hyg 1995; 52: 532–5. Tiabendazole is given orally, with meals, usually in a Infect Dis 1994; 169: 1076–9. 5. Pitisuttithum P, et al. A randomized comparative study of alben- 3. El-Karaksy H, et al. Human fascioliasis in Egyptian children: dose of 25 mg/kg twice daily for 2 or more days, the dazole and thiabendazole in chronic strongyloidiasis. Southeast successful treatment with triclabendazole. J Trop Pediatr 1999; duration depending on the type of infection; the daily Asian J Trop Med Public Health 1995; 26: 735–8. 45: 135–8. 6. Schaffel R, et al. Thiabendazole for the treatment of strongyloi- dose should not exceed 3 g. For those unable to tolerate diasis in patients with hematologic malignancies. Clin Infect Dis 4. Millán JC, et al. The efficacy and tolerability of triclabendazole 2000; 31: 821–2. in Cuban patients with latent and chronic Fasciola hepatica in- 2 doses daily, 25 mg/kg may be given after the largest fection. Am J Trop Med Hyg 2000; 63: 264–9. Syngamosis. Tiabendazole has been used successfully1,2 to meal on day 1 and repeated 24 hours later after a simi- 5. Graham CS, et al. Imported Fasciola hepatica infection in the lar meal on day 2. For mass treatment, a single dose of treat syngamosis (p.138) when it has occurred in man. United States and treatment with triclabendazole. Clin Infect Dis 1. Grell GAC, et al. Syngamus in a West Indian. BMJ 1978; 2: 2001; 33: 1–5. 50 mg/kg after the evening meal is suggested although 1464. the incidence of adverse effects may be higher than 2. Leers W-D, et al. Syngamosis, an unusual case of asthma: the 6. Talaie H, et al. Randomized trial of a single, double and triple first reported case in Canada. Can Med Assoc J 1985; 132: dose of 10 mg/kg of a human formulation of triclabendazole in with 2 doses of 25 mg/kg. 269–70. patients with fascioliasis. Clin Exp Pharmacol Physiol 2004; 31: In , 25 mg/kg may be given 777–82. Preparations 7. Marcos LA, et al. Natural history, clinicoradiologic correlates, twice daily for 2 days, repeated after 2 days if neces- BP 2008: Tiabendazole Tablets; and response to triclabendazole in acute massive fascioliasis. Am sary; topical treatment with a 10 to 15% suspension in- USP 31: Thiabendazole Oral Suspension; Thiabendazole Tablets. J Trop Med Hyg 2008; 78: 222–7. tended for oral use has also been advocated as an alter- Proprietary Preparations (details are given in Part 3) Arg.: Foldan; Austral.: Mintezol; Braz.: Benzol†; Foldan; Thiaben†; Thi- Lung fluke infections. Encouraging results were reported native or adjunct to oral treatment. anax; Tiabenzol†; Tiadol; Tiaplex; Chile: Soldrin; Gr.: Mintezol; Mex.: from a pilot study of triclabendazole1 in the treatment of para- In dracunculiasis, 25 to 50 mg/kg may be given twice Eprofil; Spain: Tr iasox†; USA: Mintezol; Venez.: Drofen†. gonimiasis (p.137). In an open comparative study2 in 62 patients, Multi-ingredient: Braz.: Derms; Eraverm-T†; Folderm Pomada; For- a more rapid parasitological response was obtained with tricla- daily for one day; in massive infection a further verm; Helmi-Ped†; Helmib†; Helmiben; Helmidrax†; Josverm†; Metiaben†; bendazole in oral doses of 5 mg/kg once daily for 3 days, 50 mg/kg may be given after 5 to 8 days. Micoplex; Neovermin; Octelmin†; Poliben†; Profium; Prohelmin†; Thiabe- na†; Vermilen Composto†; Vermol†; Zoles†. 10 mg/kg twice on one day, or 10 mg/kg as a single dose, than In strongyloidiasis, 25 mg/kg may be given twice daily with praziquantel. Clinical symptoms resolved at a comparable rate in all groups. A later study compared the two one-day regi- for 2 or 3 days or 50 mg/kg as a single dose; when the mens in 154 patients.3 After 3 months, the cure rates (assessed by infection is disseminated treatment for at least 5 days Triclabendazole (BAN, rINN) clearance of eggs from sputum) were 84.4% in those given a may be necessary. Triclabendazol; Triclabendazolum. 5-Chloro-6-(2,3-dichlorophe- single dose of 10 mg/kg, and 90.9% in those given two such dos- noxy)-2-(methylthio)benzimidazole. es on the same day. In those who were still infected at 3 months, In trichinosis, 25 mg/kg may be given twice daily for 2 Триклабендазол a second two-dose course resulted in complete parasitological to 4 successive days. clearance at 1 year. C14H9Cl3N2OS = 359.7. In toxocariasis, 25 mg/kg may be given twice daily for CAS — 68786-66-3. 1. Ripert C, et al. Therapeutic effect of triclabendazole in patients ATC — P02BX04. with paragonimiasis in Cameroon: a pilot study. Trans R Soc 5 to 7 days. ATC Vet — QP52AC01. Trop Med Hyg 1992; 86: 417. Tiabendazole also has some activity. It is 2. Calvopiña M, et al. Treatment of human pulmonary paragonim- used as a fungicidal preservative for certain foods. iasis with triclabendazole: clinical tolerance and drug efficacy. Cl Trans R Soc Trop Med Hyg 1998; 92: 566–9. 1,2 3. Calvopiña M, et al. Comparison of two single-day regimens of Dracunculiasis. Tiabendazole may be used for symptomatic H OCl treatment of dracunculiasis (p.136), although it has no direct an- H3C N triclabendazole for the treatment of human pulmonary parag- onimiasis. Trans R Soc Trop Med Hyg 2003; 97: 451–4. thelmintic effect. It is used to facilitate removal of the worm from S subcutaneous tissues. N Cl Preparations 1. Muller R. Guinea worm disease: epidemiology, control, and treatment. Bull WHO 1979; 57: 683–9. Proprietary Preparations (details are given in Part 3) 2. Kale OO, et al. Controlled comparative trial of thiabendazole Profile Fr.: Egaten. and metronidazole in the treatment of dracontiasis. Ann Trop Triclabendazole is a benzimidazole anthelmintic used in veteri- Med Parasitol 1983; 77: 151–7. nary medicine for the treatment of fascioliasis. It is also increas-

The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)