Aluminium Hydroxide

(USAN, pINN)
Synonyms: Aliuminio hidroksidas; Alumiinihydroksidi; Aluminii Hydroxidum; Aluminii oxidum hydricum; Aluminium Oxidum Hydricum; Aluminium (oxyde d’) hydraté; Aluminiumhydroxid; Aluminum Hydroxide; Alüminyum Hidroksit; Glinu wodorotlenek; Hidróxido de aluminio; Hydroxid hlinitý; Wasserhaltiges Aluminiumoxid.
Cyrillic synonym: Алюминий Гидроксид.

💊 Chemical information

CAS — 21645-51-2 [Al(OH) 3 ].
ATC — A02AB01.
ATC Vet — QA02AB01.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, US, and Viet.

Ph. Eur. 6.2 (Aluminium Oxide, Hydrated; Dried Aluminium Hydroxide BP 2008). It contains the equivalent of 47 to 60% Al 2 O 3 . It is a white or almost white, amorphous powder. Practically insoluble in water; it dissolves in dilute mineral acids and in solutions of alkali hydroxides. Store in airtight containers at a temperature not exceeding 30°.

Ph. Eur. 6.2 (Aluminium Hydroxide, Hydrated, for Adsorption; Aluminii Hydroxidum Hydricum ad Adsorptionem). A white or almost white, translucent, viscous, colloidal gel. A supernatant may be formed upon standing. A clear or almost clear solution is obtained with alkali hydroxide solutions and with mineral acids. pH 5.5 to 8.5. Store at a temperature not exceeding 30°. Do not allow to freeze.

USP 31 (Aluminum Hydroxide Gel). A suspension of amorphous aluminium hydroxide in which there is a partial substitution of carbonate for hydroxide. It is a white viscous suspension from which small amounts of clear liquid may separate on standing. It has a pH of between 5.5 and 8.0. Store in airtight containers. Avoid freezing.

USP 31 (Dried Aluminum Hydroxide Gel). An amorphous form of aluminium hydroxide in which there is a partial substitution of carbonate for hydroxide. It contains the equivalent of not less than 76.5% of Al(OH) 3 and may contain varying quantities of basic aluminium carbonate and bicarbonate. The labelling requirements states that 1 g of dried aluminium hydroxide gel is equivalent to 765 mg of Al(OH) 3 . It is a white, odourless, tasteless, amorphous powder. Insoluble in water and in alcohol; soluble in dilute mineral acids and in solutions of fixed alkali hydroxides. A 4% aqueous dispersion has a pH of not more than 10.0. Store in airtight containers.

💊 Adverse Effects and Precautions

Aluminium hydroxide, like other aluminium compounds, is astringent and may cause constipation; large doses can cause intestinal obstruction. Excessive doses, or even normal doses in patients with low-phosphate diets, may lead to phosphate depletion accompanied by increased bone resorption and hypercalciuria with the risk of osteomalacia. Aluminium salts are not, in general, well absorbed from the gastrointestinal tract, and systemic effects are therefore rare in patients with normal renal function. However, care is necessary in patients with chronic renal impairment: osteomalacia or adynamic bone disease, encephalopathy, dementia, and microcytic hypochromic anaemia have been associated with aluminium accumulation in such patients given large doses of aluminium hydroxide as a phosphate-binding agent. Similar adverse effects have also been associated with the aluminium content of dialysis fluids. Aluminium hydroxide used as an adjuvant in adsorbed vaccines has been associated with the formation of granulomas.

Children.

For the suggestion that aluminium-containing antacids should not be used in infants, see Toxicity, below.

Porphyria.

Aluminium hydroxide is considered by some to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals. UK licensed product information states that aluminium hydroxide may be unsafe in patients with porphyria undergoing haemodialysis. To x i c i t y . References to aluminium toxicity in dialysis patients and the possible association between aluminium ingestion and Alzheimer’s disease are included under Aluminium. Aluminium accumulation does not generally appear to be significant in patients with normal renal function taking therapeutic doses of aluminium-containing antacids, and there is little evidence that such antacids are a risk factor for Alzheimer’s disease.1 Elevated plasma-aluminium concentrations have been reported in infants with normal renal function given aluminiumcontaining antacids but there were no obvious signs of toxicity.2There have, however, been reports of phosphate depletion and rickets in a few infants caused by the use of antacids containing magnesium and aluminium hydroxides. In these cases the antacid had been started within a few months of birth and continued for up to 8 months. In reports that described a total of 3 infants,3,4the authors suggested that the use of soya-based infant feeding formulas, the phytates of which can interfere with mineral ab sorption, may have exacerbated the phosphate-binding effect of the antacid. In another case5 a dosing error resulted in the infant receiving an excessive dose of antacid for 6 months. The BNFC advises against the use of any aluminium-containing antacid in neonates and infants. Aluminium accumulation resulting in osteomalacia or encephalopathy with seizures and dementia has been reported in children with renal failure (but not on dialysis) treated with aluminiumcontaining phosphate binders.6-10 In an adult male patient with severe chronic renal failure who was not on dialysis, self-medication with antacids for at least 3 years resulted in aluminium toxicity associated with encephalopathy, bone disease, and microcytic anaemia.11 Aluminium-containing antacids should therefore be used with caution in patients with chronic renal failure, especially in children. Oral citrate salts increase the absorption of aluminium from the gastrointestinal tract12 and patients with renal failure taking aluminium compounds should avoid citrate-containing preparations, which include many effervescent or dispersible tablets.13,14 Interactions can be minimised by giving the aluminium compound and any other medication 2 to 3 hours apart. The absorption of aluminium from the gastrointestinal tract may be enhanced if aluminium compounds are taken with citrates or ascorbic acid (see Toxicity, above).

💊 Pharmacokinetics

Aluminium hydroxide, given orally, slowly reacts with the hydrochloric acid in the stomach to form soluble aluminium chloride, some of which is absorbed. The presence of food or other factors that decrease gastric emptying prolongs the availability of aluminium hydroxide to react and may increase the amount of aluminium chloride formed. About 100 to 500 micrograms of the cation is reported to be absorbed from standard daily doses of an aluminiumcontaining antacid, leading to about a doubling of usual aluminium concentrations in the plasma of patients with normal renal function. Absorbed aluminium is eliminated in the urine, and patients with renal failure are therefore at particular risk of accumulation (especially in bone and the CNS), and aluminium toxicity (see above). The aluminium compounds remaining in the gastrointestinal tract, which account for most of a dose, form insoluble, poorly absorbed aluminium salts in the intestines including hydroxides, carbonates, phosphates and fatty acid derivatives, which are excreted in the faeces.

💊 Uses and Administration

Aluminium hydroxide is used as an antacid. It is given orally in doses of up to about 1 g, between meals and at bedtime. In order to reduce the constipating effects, aluminium hydroxide is often given with a magnesium-containing antacid, such as magnesium oxide or magnesium hydroxide. Aluminium hydroxide binds phosphate in the gastrointestinal tract to form insoluble complexes and reduces phosphate absorption. It may thus be used to treat hyperphosphataemia in patients with chronic renal failure or associated secondary hyperparathyroidism. With this use the dose must be adjusted to the individual patient’s requirement but up to about 10 g daily may be given orally in divided doses with meals. Aluminium hydroxide is also used as an adjuvant in adsorbed vaccines.

Polymyositis and dermatomyositis.

Corticosteroids form the basis of the management of polymyositis but the calcinosis that may occur in dermatomyositis does not always respond well. Aluminium hydroxide 1.68 to 2.24 g daily produced clinical improvement with complete clearing of most calcified nodules after 1 year in a patient with calcinosis cutis complicating juvenile dermatomyositis.1 The calcified masses are made up of hydroxyapatite and amorphous calcium phosphate and reduction in phosphate absorption by aluminium hydroxide probably helped to reverse their formation. Subsequent cases2,3have also reported benefit from aluminium hydroxide treatment in the management of calcinosis.
1. Wang W-J, et al. Calcinosis cutis in juvenile dermatomyositis: remarkable response to aluminium hydroxide therapy. Arch Dermatol 1988; 124: 1721–2
2. Nakagawa T, Takaiwa T. Calcinosis cutis in juvenile dermatomyositis responsive to aluminium hydroxide treatment. J Dermatol 1993; 20: 558–60
3. Wananukul S, et al. Calcinosis cutis presenting years before other clinical manifestations of juvenile dermatomyositis: report of two cases. Australas J Dermatol 1997; 38: 202–5.

💊 Preparations

BP 2008: Aluminium Hydroxide Oral Suspension; Aluminium Hydroxide Tablets; Co-magaldrox Oral Suspension; Co-magaldrox Tablets; Compound Magnesium Trisilicate Tablets; USP 31: Alumina and Magnesia Oral Suspension; Alumina and Magnesia Tablets; Alumina and Magnesium Carbonate Oral Suspension; Alumina and Magnesium Carbonate Tablets; Alumina and Magnesium Trisilicate Oral Suspension; Alumina and Magnesium Trisilicate Tablets; Alumina, Magnesia, and Calcium Carbonate Oral Suspension; Alumina, Magnesia, and Calcium Carbonate Tablets; Alumina, Magnesia, and Simethicone Oral Suspension; Alumina, Magnesia, and Simethicone Tablets; Alumina, Magnesia, Calcium Carbonate, and Simethicone Tablets; Alumina, Magnesium Carbonate, and Magnesium Oxide Tablets; Aluminum Hydroxide Gel; Aspirin, Alumina, and Magnesia Tablets; Aspirin, Alumina, and Magnesium Oxide Tablets; Dried Aluminum Hydroxide Gel; Dried Aluminum Hydroxide Gel Capsules; Dried Aluminum Hydroxide Gel Tablets.

Proprietary Preparations

Arg.: Pepsamar; Austral.: Alu-Tab; Austria: Anti-Phosphat; Braz.: Aludroxil; Aziram; Biodrox†; Ductogel; Fluagel†; Gastromax; Gastrox; Gelpan†; Hidroxialiv†; Kaogel†; Mylanta Plus; Natusgel†; Noacid†; Pepsamar; Peptgel; Canad.: Alu-Tab†; Alugel; Amphojel; Basaljel; Chile: Risthal†; Ger.: Aludrox; Anti-Phosphat; Gr.: Alu-Cap; Pepsamar; Hong Kong: AluTa b ; India: Aludrox; Tricaine-MPS; Irl.: Aludrox; Israel: Alu-Cap; Ital.: Polisilon†; Malaysia: Alu-Tab; Mex.: Domigel; Magnalum†; NZ: Alu-Tab; Amphojel†; Philipp.: Alu-Tab; Pol.: Alusal; Port.: Gelumina†; Pepsamar; S.Afr.: Alukon; Amphojel; Singapore: Alu-Tab; Spain: Alugel; Pepsamar; Switz.: Anti-phosphate; Gastracol; UK: Alu-Cap; Aludrox†; USA: ALternaGEL; Alu-Cap†; Alu-Tab; Amphojel; Dialume; Nephrox; Venez.: Gelidral†. Used as an adjunct in: Arg.: Dristan Analgesico†; Dristan Compuesto; Truxa R†; Braz.: Analtrix†; Butazolon†; Posdrink; Redentil†; Resprax; Canad.: C2 with Codeine†; Chile: Silartrin†; Fr.: Finidol†; Gr.: Ascriptin†; Indon.: Naspro; Israel: Ascriptin†; Ital.: Ascriptin; Via Mal; Mex.: Ascriptin; Meprosona-F; Switz.: Alcacyl; Contre-Douleurs plus; Contre-Douleurs†; USA: Arthritis Pain Formula; Ascriptin; Asprimox; Cama Arthritis Pain Reliever; Cope; Magnaprin†; Vanquish; Venez.: Ascriptin.
Published November 04, 2018.