1722 Gastrointestinal Drugs Clebopride (BAN, USAN, rINN) Pharmacopoeias. In US. ical evidence had increased and dantron was now established as USP 31 (Clidinium Bromide). A white or nearly white, practical- a potential human carcinogen.5 Cleboprida; Clébopride; Clebopridum; LAS-9273. 4-Amino-N- ly odourless, crystalline powder. Soluble in water and in alcohol; 1. Tolman KG, et al. Possible hepatotoxicity of Doxidan. Ann In- (1-benzyl-4-piperidyl)-5-chloro-o-anisamide. slightly soluble in ether and in benzene. Store in airtight contain- tern Med 1976; 84: 290–2. Клебоприд ers. Protect from light. 2. Darke CS, Cooper RG. Unusual case of skin discoloration. BMJ 1978; 1: 1188–9. C20H24ClN3O2 = 373.9. Profile 3. Greer IA. Orange periods. BMJ 1984; 289: 323. CAS — 55905-53-8. Clidinium bromide is a quaternary ammonium antimuscarinic 4. Patel PM, et al. Anthraquinone laxatives and human cancer: an association in one case. Postgrad Med J 1989; 65: 216–17. ATC — A03FA06. with peripheral effects similar to those of atropine (p.1219). It 5. Committee on Safety of Medicines/Medicine Control Agency. ATC Vet — QA03FA06. has been used alone or more often with chlordiazepoxide in the Danthron restricted to constipation in the terminally ill. Current symptomatic treatment of peptic ulcer disease and other gas- Problems 2000; 26: 4. Also available at: http:// trointestinal disorders. www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE& dDocName=CON007462&RevisionSelectionMethod= Cl Preparations LatestReleased (accessed 08/11/06) USP 31: Chlordiazepoxide Hydrochloride and Clidinium Bromide Cap- 1 H2N Breast feeding. The American Academy of Pediatrics state sules. that, although usually compatible with breast feeding, use of dan- H Proprietary Preparations (details are given in Part 3) tron by breast-feeding mothers has been reported to cause in- N Multi-ingredient: Arg.: Libraxin; Canad.: Apo-Chlorax; Librax; Chile: creased bowel activity in the infant. Gastrolen; Lerogin; Libraxin; Lironex†; Sedogastrol†; Tensoliv; Fin.: Librax; 1. American Academy of Pediatrics. The transfer of drugs and oth- Fr.: Librax; Gr.: Distedon; Librax; Hong Kong: Bralix; Librax; Medocalum†; er chemicals into human milk. Pediatrics 2001; 108: 776–89. O O N India: Equirex; Normaxin; Spasrax; Indon.: Braxidin; Cliad; Klidibrax; Li- H C Correction. ibid.; 1029. Also available at: 3 brax; Melidox; Renagas; Israel: Nirvaxal; Ital.: Librax; Malaysia: Apo- http://aappolicy.aappublications.org/cgi/content/full/ Chlorax†; Liblan; Port.: Librax; S.Afr.: Librax; Singapore: Apo-Chlorax; pediatrics%3b108/3/776 (accessed 08/11/06) Chlobax; Librax; Medocalum; Switz.: Librax; Librocol; Thai.: Kenspa; Li- brax; Pobrax†; Tumax; Zepobrax†; Turk.: Klipaks; Librax; USA: Clindex; Pharmacokinetics Clebopride Malate (BANM, rINNM) Librax; Venez.: Librax. Dantron is metabolised by bacteria in the colon. Dantron or its Clébopride, malate de; Clebopridi malas; Kleboprid malát; Kle- metabolites are absorbed from the gastrointestinal tract, as indi- bopridimalaatti; Klebopridmalat; Kleboprid-malát; Kleboprido cated by discoloration of urine in some patients. Dantron or its malatas; Malato de cleboprida. metabolites are excreted in the faeces and the urine, and also in Colocynth other secretions including breast milk. Клебоприда Малат Bitter Apple; Bitter Cucumber; Colocinto; Colocynth Pulp; Colo- Uses and Administration C20H24ClN3O2,C4H6O5 = 508.0. cynthis; Coloquinte; Coloquintidas; Koloquinthen. Dantron is an anthraquinone stimulant laxative but, unlike senna CAS — 57645-91-7. Колоцинт (p.1769), it is not a glycoside. It is given orally to treat constipa- ATC — A03FA06. tion (p.1693) and is effective within 6 to 12 hours. However, be- ATC Vet — QA03FA06. NOTE. The synonym Bitter Apple has also been applied to the cause of concern over rodent carcinogenicity it has been with- fruits of Solanum incanum. Pharmacopoeias. In Eur. (see p.vii). drawn in some countries, and its use restricted in others. In the Ph. Eur. 6.2 (Clebopride Malate). A white or almost white, crys- Profile UK, it may be used only in terminally ill patients. talline powder. Sparingly soluble in water and in methyl alcohol; Colocynth is the dried pulp of the fruit of Citrullus colocynthis Dantron is given in doses of 25 to 75 mg when given with (Cucurbitaceae). It has a drastic purgative and irritant action and slightly soluble in dehydrated alcohol; practically insoluble in poloxamer 188 (p.1918) as co-danthramer, and in doses of 50 to has been superseded by less toxic laxatives. dichloromethane. The pH of a 1% solution in water is 3.8 to 4.2. 150 mg when given with docusate sodium (p.1725) as co-dan- Protect from light. Homoeopathy. Colocynth has been used in homoeopathic thrusate. Doses are usually given at bedtime. For doses in chil- medicines under the following names: Colocynthis; Coloc. dren, see below. Profile Administration in children. Children under 12 years have Clebopride is a substituted benzamide similar to metoclopramide been given dantron 12.5 to 25 mg orally as co-danthramer or (p.1747), that is used for its antiemetic and prokinetic actions in 50 mg as co-danthrusate. Doses are usually given at bedtime. nausea and vomiting (p.1700) and various other gastrointestinal Dantron (BAN, rINN) Children aged 12 years and over may be treated with the adult disorders. It is given as the malate but doses are expressed in Antrapurol; Chrysazin; Danthron; Dantrón; Dantrone; Dantroni; dose (see Uses and Administration, above). terms of the base. Clebopride malate 679 micrograms is equiva- lent to about 500 micrograms of clebopride. Dantronum; Dianthon; Dioxyanthrachinonum. 1,8-Dihydroxyan- The BNFC recommends similar doses to these, but restricts the thraquinone. use of co-danthramer to children aged 2 years and over, and the Clebopride malate is given in a usual oral dose equivalent to use of co-danthrusate to those aged 6 years and over. clebopride 0.5 mg three times daily before meals or 0.5 to 1 mg Дантрон C H O = 240.2. Dantron should not be used in infants wearing nappies (diapers) by intramuscular or intravenous injection for acute symptoms. 14 8 4 as it may cause discoloration and superficial sloughing of the For dosage in children see below. CAS — 117-10-2. skin. ATC — A06AB03. Administration in children. Adolescents aged 12 to 20 years ATC Vet — QA06AB03. Preparations may be given clebopride malate orally in a dose equivalent to BP 2008: Co-danthrusate Capsules. clebopride 250 micrograms three times daily. An oral dose of 15 (details are given in Part 3) to 20 micrograms/kg daily in 3 divided doses may be used for Proprietary Preparations OH OHO children under 12; the following doses have been recommended: Multi-ingredient: Braz.: Fenogar†; Chile: Modane; Irl.: Ailax; Codalax; Cotron; Mex.: Modaton; NZ: Codalax†; Conthram†; UK: Ailax†; Capsu- • 1 to 4 years: 50 micrograms 3 times daily vac; Codalax; Danlax; Normax. • 4 to 8 years: 100 micrograms 3 times daily • 8 to 10 years: 150 micrograms 3 times daily • 10 to 12 years: 200 micrograms 3 times daily Dicycloverine Hydrochloride Preparations O (BANM, rINNM) Proprietary Preparations (details are given in Part 3) NOTE. Compounded preparations of dantron may be represented Cloridrato de Dicicloverina; Dicikloverin-hidroklorid; Dicikloveri- Arg.: Gastridin; Indon.: Clast; Ital.: Motilex; Port.: Clebofex; Clebutec; by the following names: no hidrochloridas; Dicyclomine Hydrochloride; Dicyclovérine, Spain: Cleboril. chlorhydrate de; Dicycloverini hydrochloridum; Dicykloverin-hy- • Co-danthramer x/y (BAN)—where x and y are the strengths in Multi-ingredient: Arg.: Eudon; Gastridin-E; Somasedan; Spain: Clanzo- drochlorid; Dicykloverinhydroklorid; Disykloveriinihydrokloridi; flat; Flatoril. milligrams of dantron and poloxamer respectively Hidrocloruro de dicicloverina. 2-Diethylaminoethyl bicyclohexyl- • Co-danthrusate (BAN)—dantron 5 parts and docusate sodium 1-carboxylate hydrochloride. 6 parts (w/w). Дицикловерина Гидрохлорид Pharmacopoeias. In Br. Clidinium Bromide (BAN, USAN, rINN) C19H35NO2,HCl = 345.9. BP 2008 (Dantron). An orange, odourless or almost odourless, Bromuro de clidinio; Clidinii Bromidum; Clidinium, Bromure de; CAS — 77-19-0 (dicycloverine); 67-92-5 (dicycloverine hy- crystalline powder. Practically insoluble in water; very slightly drochloride). Klidiniumbromid; Klidiniumbromidi; Klidinyum Bromür; Ro-2- soluble in alcohol; soluble in chloroform; slightly soluble in ATC — A03AA07. 3773. 3-Benziloyloxy-1-methylquinuclidinium bromide. ether; dissolves in solutions of alkali hydroxides. ATC Vet — QA03AA07. Клидиния Бромид Adverse Effects and Precautions C22H26BrNO3 = 432.4. As for Senna, p.1769. Dantron may colour the urine pink or red. CAS — 7020-55-5 (clidinium); 3485-62-9 (clidinium bro- Discoloration and superficial sloughing of perianal skin can oc- CH3 mide). cur after prolonged contact, therefore dantron should not be used O in infants wearing nappies (diapers) and should be used with cau- tion in incontinent patients. The mucosa of the large intestine N CH3 O CH3 may be discoloured with prolonged use or high dosage. + In rodents, dantron has been associated with the development of N intestinal and liver tumours. Consequently, its use has been re- O stricted, see Uses and Administration, below. − (dicycloverine) Br ◊ References to adverse effects occurring with dantron-contain- O ing laxatives include individual cases of leucopenia with liver 1 2 Pharmacopoeias. In Eur. (see p.vii) and US. OH damage, greyish-blue skin discoloration, and orange vaginal