1706 Gastrointestinal Drugs

US market) were estimated to represent a rate of 1 case per Basic Aluminium Carbonate NOTE. Algeldrate (USAN, pINN) is defined as a hydrated alumin- 1000 patient-years. Serious complications of constipation did ium hydroxide with the general formula of Al(OH)3,xH2O. not seem to be increased in the population of alosetron users. Aluminium Hydroxycarbonate; Aluminum Carbonate, Basic Compounded preparations of aluminium hydroxide may be rep- (USAN); Carbonato básico de aluminio. 1. Chang L, et al. Incidence of ischemic colitis and serious compli- resented by the following names: cations of constipation among patients using alosetron: system- Основный Углекислый Алюминий • Co-magaldrox x/y (BAN)—where x and y are the strengths in atic review of clinical trials and post-marketing surveillance da- milligrams of magnesium hydroxide and aluminium hydrox- ta. Am J Gastroenterol 2006; 101: 1069–79. Profile Basic aluminium carbonate is a combination of aluminium hy- ide respectively. Precautions droxide and aluminium carbonate. It is an antacid with general Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, US, and Alosetron should be stopped immediately in patients who devel- properties similar to those of aluminium hydroxide (below). Viet. op constipation or symptoms of ischaemic colitis such as new or Ph. Eur. 6.2 (Aluminium Oxide, Hydrated; Dried Aluminium Hy- worsening abdominal pain or blood in the stool. Treatment with Basic aluminium carbonate has also been given orally as a phos- phate binder in the treatment of hyperphosphataemia. For a dis- droxide BP 2008). It contains the equivalent of 47 to 60% Al2O3. alosetron should not be resumed in patients who develop ischae- It is a white or almost white, amorphous powder. Practically in- mic colitis. cussion of the choice of phosphate binders, see Renal Osteodys- trophy, p.1086. soluble in water; it dissolves in dilute mineral acids and in solu- Alosetron should not be used in patients with a history of severe tions of alkali hydroxides. Store in airtight containers at a tem- or chronic constipation, intestinal obstruction or stricture, toxic Preparations perature not exceeding 30°. megacolon, or gastrointestinal perforation or adhesions. It is also Proprietary Preparations (details are given in Part 3) Ph. Eur. 6.2 (Aluminium Hydroxide, Hydrated, for Adsorption; contra-indicated in patients with a history of ischaemic colitis, Multi-ingredient: Port.: Gastropensan. Aluminii Hydroxidum Hydricum ad Adsorptionem). A white or impaired intestinal circulation, thrombophlebitis, or hypercoagu- almost white, translucent, viscous, colloidal gel. A supernatant lable state, and those with current or previous inflammatory may be formed upon standing. A clear or almost clear solution is bowel disease or diverticulitis. obtained with alkali hydroxide solutions and with mineral acids. Alosetron should not be used in those with severe hepatic impair- Aluminium Formate pH 5.5 to 8.5. Store at a temperature not exceeding 30°. Do not ment or a history thereof; it should be used with caution in pa- Aluminium Triformate. allow to freeze. tients with mild to moderate hepatic impairment. Elderly patients USP 31 (Aluminum Hydroxide Gel). A suspension of amor- may be at increased risk of severe complications if constipation Муравьинокислый Алюминий; Формиат Алюминия phous aluminium hydroxide in which there is a partial substitu- develops. Al(CHO2)3,3H2O = 216.1. tion of carbonate for hydroxide. It is a white viscous suspension CAS — 7360-53-4 (anhydrous aluminium formate). from which small amounts of clear liquid may separate on stand- Interactions ing. It has a pH of between 5.5 and 8.0. Store in airtight contain- Plasma concentrations of alosetron are markedly increased, and Profile ers. Avoid freezing. Aluminium formate has astringent properties and has been used its half-life prolonged roughly threefold, when given with flu- USP 31 (Dried Aluminum Hydroxide Gel). An amorphous form in topical preparations for mouth disorders. voxamine; such a combination should be avoided. Licensed of aluminium hydroxide in which there is a partial substitution of product information recommends that use with other more mod- Preparations carbonate for hydroxide. It contains the equivalent of not less erate inhibitors of cytochrome P450 isoenzyme CYP1A2 (such than 76.5% of Al(OH) and may contain varying quantities of as quinolone antibacterials and cimetidine) should be avoided Proprietary Preparations (details are given in Part 3) 3 Ger.: Dynexan Zahnfleischtropfen. basic aluminium carbonate and bicarbonate. The labelling re- unless clinically necessary, because of the risk of similar interac- quirements states that 1 g of dried aluminium hydroxide gel is tions. Ketoconazole also increases plasma alosetron concentra- Multi-ingredient: Austria: Cional; Dynexan; Methyment; S.Afr.: Dynex- an. equivalent to 765 mg of Al(OH)3. It is a white, odourless, taste- tions; care should be taken if alosetron is used with this or other less, amorphous powder. Insoluble in water and in alcohol; solu- potent inhibitors of the CYP3A4 isoenzyme (including clarithro- ble in dilute mineral acids and in solutions of fixed alkali hydrox- mycin, telithromycin, HIV-protease inhibitors, voriconazole, and ides. A 4% aqueous dispersion has a pH of not more than 10.0. itraconazole). Aluminium Glycinate Store in airtight containers. Pharmacokinetics Aluminio, glicinato de; Basic Aluminium Aminoacetate; Dihy- Alosetron is rapidly absorbed from the gastrointestinal tract; droxyaluminum Aminoacetate. (Glycinato-N,O)dihydroxyalu- Adverse Effects and Precautions peak plasma concentrations are reached about 1 hour after an minium hydrate. Aluminium hydroxide, like other aluminium com- oral dose. Plasma concentrations are 30 to 50% lower in men than in women given the same oral dose; clearance is lower in Алюминия Глицинат pounds, is astringent and may cause constipation; large women. Bioavailability is about 60%; the extent and rate of ab- C2H6AlNO4(+xH2O) = 135.1 (anhydrous). doses can cause intestinal obstruction. sorption are slightly reduced by food. Plasma protein binding is CAS — 13682-92-3 (anhydrous aluminium glycinate); Excessive doses, or even normal doses in patients with about 82%. Alosetron is extensively metabolised via cytochrome 41354-48-7 (aluminium glycinate hydrate). low-phosphate diets, may lead to phosphate depletion P450 isoenzymes, particularly CYP1A2, although CYP2C9 and ATC — A02AB07. accompanied by increased bone resorption and hyper- CYP3A4 also play a role. Numerous metabolites are excreted in ATC Vet — QA02AB07. the urine and faeces; only 6% of a dose is recovered unchanged calciuria with the risk of osteomalacia. Pharmacopoeias. In Br. and US. from the urine. The terminal elimination half-life of alosetron is Aluminium salts are not, in general, well absorbed reported to be about 1.5 hours. BP 2008 (Aluminium Glycinate). A white or almost white, odourless or almost odourless, powder. It contains 34.5 to 38.5% from the gastrointestinal tract, and systemic effects are ◊ References. of Al2O3 calculated on the dried substance, and not more than therefore rare in patients with normal renal function. 1. Koch KM, et al. Sex and age differences in the pharmacokinetics 12% loss of weight on drying. Practically insoluble in water and However, care is necessary in patients with chronic of alosetron. Br J Clin Pharmacol 2002; 53: 238–42. in organic solvents; it dissolves in dilute mineral acids and in renal impairment: osteomalacia or adynamic bone Uses and Administration aqueous solutions of alkali hydroxides. A 4% suspension in wa- ter has a pH of 6.5 to 7.5. disease, encephalopathy, dementia, and microcytic Alosetron is a 5-HT3 antagonist used in the treatment of severe diarrhoea-predominant irritable bowel syndrome (p.1699) in USP 31 (Dihydroxyaluminum Aminoacetate). A white, odour- hypochromic anaemia have been associated with alu- women who have not responded to conventional therapy; effec- less, powder. It may contain small amounts of aluminium oxide minium accumulation in such patients given large dos- tiveness in men has not been established. It is given orally as the and aminoacetic acid. It loses not more than 14.5% of its weight es of aluminium hydroxide as a phosphate-binding hydrochloride but doses are expressed in terms of the base; alo- on drying. Insoluble in water and in organic solvents; soluble in dilute mineral acids and in solutions of fixed alkalis. A 4% sus- agent. Similar adverse effects have also been associat- setron hydrochloride 1.12 mg is equivalent to about 1 mg of alo- ed with the aluminium content of dialysis fluids. setron. pension in water has a pH of 6.5 to 7.5. The initial dose is the equivalent of alosetron 500 micrograms Profile Aluminium hydroxide used as an adjuvant in adsorbed twice daily for 4 weeks; if tolerated, the dose may then be in- Aluminium glycinate is an antacid with general properties simi- vaccines has been associated with the formation of creased if necessary to 1 mg twice daily. If symptoms are not ad- lar to those of aluminium hydroxide (below). It has been given in granulomas. equately controlled after 4 weeks of treatment with the higher doses of up to 1 g by mouth. Children. For the suggestion that aluminium-containing antac- dose, alosetron should be stopped. Preparations ids should not be used in infants, see Toxicity, below. ◊ References. USP 31: Dihydroxyaluminum Aminoacetate Magma. Porphyria. Aluminium hydroxide is considered by some to be 1. Lembo A, et al. Alosetron in irritable bowel syndrome: strategies Proprietary Preparations (details are given in Part 3) unsafe in patients with porphyria because it has been shown to be for its use in a common gastrointestinal disorder. Drugs 2003; Denm.: Almin. porphyrinogenic in animals. 63: 1895–1905. 2. Mayer EA, Bradesi S. Alosetron and irritable bowel syndrome. Multi-ingredient: Arg.: Dafne; Austria: Gastripan; Belg.: Alucid; Chile: UK licensed product information states that aluminium hydrox- Expert Opin Pharmacother 2003; 4: 2089–98. Sinacid; Denm.: Alminox; Fr.: Acidrine; Ger.: Acidrine†; Gr.: Novalox; In- ide may be unsafe in patients with porphyria undergoing haemo- don.: Acidrine; Ital.: Acidrine; Pol.: Proacid; Spain: Gastroglutal†; Meteo- dialysis. 3. Cremonini F, et al. Efficacy of alosetron in irritable bowel syn- ril; Natrocitral; Secrepat. drome: a meta-analysis of randomized controlled trials. Neuro- gastroenterol Motil 2003; 15: 79–86. Used as an adjunct in: Austria: Ambene N; Indobene; Braz.: Reumix†; So- To x i c i t y. References to aluminium toxicity in dialysis patients 4. Andresen V, Hollerbach S. Reassessing the benefits and risks of malgin; Chile: Butartrol; Flexono; Ger.: Indomet-ratiopharm m†; Ital.: As- and the possible association between aluminium ingestion and alosetron: what is its place in the treatment of irritable bowel pirina 03; Switz.: Bonidon; USA: Buffex. Alzheimer’s disease are included under Aluminium (see syndrome? Drug Safety 2004; 27: 283–92. p.2254). 5. Lembo AJ, et al. Effect of alosetron on bowel urgency and global Aluminium accumulation does not generally appear to be signif- symptoms in women with severe, diarrhea-predominant irritable icant in patients with normal renal function taking therapeutic bowel syndrome: analysis of two controlled trials. Clin Gastro- doses of aluminium-containing antacids, and there is little evi- enterol Hepatol 2004; 2: 675–82. Aluminium Hydroxide dence that such antacids are a risk factor for Alzheimer’s dis- 6. Chey WD, et al. Long-term safety and efficacy of alosetron in Aliuminio hidroksidas; Alumiinihydroksidi; Aluminii Hydroxidum; 1 women with severe diarrhea-predominant irritable bowel syn- ease. Elevated plasma-aluminium concentrations have been re- drome. Am J Gastroenterol 2004; 99: 2195–2203. Aluminii oxidum hydricum; Aluminium Oxidum Hydricum; Alu- ported in infants with normal renal function given aluminium- 2 7. Chang L, et al. A dose-ranging, phase II study of the efficacy and minium (oxyde d’) hydraté; Aluminiumhydroxid; Aluminum Hy- containing antacids but there were no obvious signs of toxicity. safety of alosetron in men with diarrhea-predominant IBS. Am J droxide; Alüminyum Hidroksit; Glinu wodorotlenek; Hidróxido There have, however, been reports of phosphate depletion and Gastroenterol 2005; 100: 115–23. de aluminio; Hydroxid hlinitý; Wasserhaltiges Aluminiumoxid. rickets in a few infants caused by the use of antacids containing Preparations Алюминий Гидроксид magnesium and aluminium hydroxides. In these cases the antac- id had been started within a few months of birth and continued Proprietary Preparations (details are given in Part 3) CAS — 21645-51-2 [Al(OH)3]. for up to 8 months. In reports that described a total of 3 infants,3,4 Arg.: Lotronex†; Mex.: Liminos†; USA: Lotronex. ATC — A02AB01. the authors suggested that the use of soya-based infant feeding ATC Vet — QA02AB01. formulas, the phytates of which can interfere with mineral ab-