Aluminum hydroxide

Limits on what this shows

• Null findings and frequency: The Chines review abstract describes aluminum antacid hypophosphatemia as rare, and notes combining two aluminum-containing agents may raise risk [15]. No incidence estimate was retrieved. In hyperphosphatemic kidney failure, lowering phosphate is the intended effect, not a deficiency [7].
• At-risk subgroups: Infants and children given antacids for colic [18]; older adults [12]; people taking aluminum hydroxide at high dose for years, such as long-term ulcer treatment [14][17]; people using more than one aluminum-containing agent [15]; low phosphate intake per the regulatory wording [4].

Regulatory status

US OTC monograph professional labeling (21 CFR 331.80(a)(4), as returned by a summarizing fetch of eCFR): "Prolonged use of aluminum-containing antacids by normophosphatemic patients may result in hypophosphatemia if phosphate intake is not adequate." [4]. A Ghana FDA SmPC for a combination product containing dried aluminium hydroxide states hypophosphatemia in prolonged use or at high doses may increase bone resorption and cause osteomalacia [5]. The three consumer Drug Facts labels opened do not mention phosphate [1][2][3].

Population evidence

Lotz 1968 [8]: studies in three normal subjects and patients with parathyroid disease during prolonged nonabsorbable antacid treatment (magnesium-aluminum hydroxides) produced hypophosphatemia, hypophosphaturia, increased gastrointestinal and urinary calcium, skeletal resorption, debility, anorexia, weakness and bone pain (abstract level, group sizes beyond the three normal subjects not stated). Spencer 1983 [9]: aluminum in antacids binds intestinal phosphorus, markedly raising fecal phosphorus, with lower urinary and serum phosphorus. Spencer 1986 [11]: 1.8 g/day aluminum hydroxide in controlled-diet balance studies produced phosphorus depletion with negative or reduced calcium balance. Case reports (Tier B): Insogna 1980 [12], 60-year-old woman, serum phosphate 1.1 mg/dL, normal calcium 10.1 mg/dL, urine calcium 448 mg/24 h, no urinary phosphate, weakness and osteomalacia; Saadeh 1987 [14], 31-year-old woman with normal renal function, Maalox TC at least six tablets daily (each 600 mg aluminum hydroxide plus 300 mg magnesium hydroxide) for 13 years, serum phosphate 2.4 rising to 4.2 mg/dL after stopping, osteoid on 60.7% of trabecular surfaces, bone pain resolved at 6 months; Carmichael 1984 [13], 53-year-old man, osteomalacia with osteitis fibrosa and stress fractures, healed after withdrawal; Chines 1990 [15], aluminum-magnesium antacid plus sucralfate, severe hypophosphatemia, recovered after stopping; Boutsen 1996 [16], 49-year-old woman, large amounts of aluminum hydroxide antacids for years, severe hypophosphatemia with multiple fractures, marked improvement after withdrawal; Woodson 1998 [17], pharmacist on high-dose Mylanta for 8 years, hypophosphatemia, improved after stopping. Pivnick 1995 [18]: two infants with rickets from phosphate depletion after prolonged aluminum-containing antacid for colic.

Mechanism

Present and named: luminal binding of dietary phosphate, impaired absorption, then secondary rise in calcium absorption and urinary calcium with skeletal resorption [8][9][14]. The 1.8 g/day experimental dose is below the Major label maximum of 3.2 g/day (arithmetic from [1]), but the label limits maximum dosage to 2 weeks [1].

Counter-evidence held on record

Counter-evidence and confounding Most case reports involve aluminum and magnesium hydroxide mixtures [14][15][17], so a magnesium contribution cannot be excluded; the experiments in [10][11] used aluminum hydroxide alone. Case reports are selected and cannot give risk. Osteomalacia and fractures are outcomes, not phosphate or vitamin D deficiency (Hard Rule 2); phosphate itself was measured in [8][9][11][12][14]. The Saadeh case had a negative aluminum bone stain and attributed the bone disease to phosphate depletion, whereas Woodson found stainable bone aluminum with normal kidneys, so aluminum toxicity in the bone can coexist [14][17]. Framing caution This is a dose- and duration-bound depletion signal, not an effect of occasional antacid use. No phosphate supplement is recommended here; treatment of a documented deficit belongs to the prescriber.

Limits on what this shows

• Null findings: Serum calcium was normal in the cases [12][14], so circulating calcium is not the marker. In 8 chronic renal failure patients on aluminum hydroxide gel, plasma calcium rose in 2 and was unchanged in 1 (as reported in the abstract), and PTH fell in 3 [19]; that population is hyperphosphatemic and does not model the depletion syndrome. Companion markers: PTH was within the reported range in Saadeh [14] and normal in Carmichael [13], so a secondary hyperparathyroid mobilization is not what was shown.
• At-risk subgroups: Same as phosphate.

Regulatory status

Calcium is not mentioned in the consumer labels opened [1][2][3]. The SmPC links hypophosphatemia to increased bone resorption [5].

Population evidence

Spencer 1986 [11]: aluminum hydroxide 1.8 g/day in balance studies produced negative or reduced calcium balances (abstract level, group sizes not captured). Lotz 1968 [8]: hypercalciuria and skeletal calcium resorption in the phosphorus-depletion syndrome. Case data: urine calcium 448 mg/24 h with serum calcium 10.1 mg/dL [12]; in Saadeh, urine calcium fell from 542 to 43 mg/24 h after stopping, with serum calcium 9.2 to 10.2 mg/dL [14] (values via summarizing fetch tool, which garbled some units in the same text).

Mechanism

Present: phosphate depletion raises calcium absorption and urinary excretion and mobilizes skeletal calcium [8]. This is one mechanism with the phosphate entry, not a separate pathway.

Counter-evidence held on record

Counter-evidence and confounding Fracture, osteomalacia and low bone density are outcomes, not calcium deficiency (Hard Rule 2); the claim here is the measured balance and urinary loss only. Not independent of the phosphate entry (see Overlap map). Spencer's balance data are from a research ward with controlled intake, not ordinary use. Framing caution Do not read this as advice to take calcium. Calcium loss here is downstream of phosphate depletion, and the fix is addressing the antacid exposure under a prescriber.

Limits on what this shows

• Null findings: None located. No study measured caries, fluorosis or bone fluoride outcomes with aluminum hydroxide.
• At-risk subgroups: People taking therapeutic fluoride (the 1986 cohort included such patients) [11]. No other subgroup defined.

Regulatory status

Fluoride is not mentioned in the labels opened [1][2][3][4][5].

Population evidence

Spencer 1980 [10]: 30 mL three times daily (1.8 g) over several weeks under controlled diet inhibited intestinal fluoride absorption, increased fecal and decreased urinary fluoride, regardless of dietary fluoride, calcium, phosphorus or magnesium. Spencer 1986 [11]: net absorption fell by an average of 57% and plasma fluoride by 41%, including osteoporosis patients on therapeutic fluoride. Both are from the same laboratory; whether subjects overlap was not established, so they are not counted as fully independent. Numbers via OpenAlex-reconstructed abstracts.

Mechanism

Aluminum inhibits intestinal fluoride absorption (abstract wording) [10]; the binding chemistry is not described in the text retrieved.

Counter-evidence held on record

Counter-evidence and confounding Fluoride is not classically essential and the clinical significance of lower absorption is unknown. The studies used a defined research diet and 1.8 g/day, so effects at occasional antacid doses are not shown. Aluminum hydroxide also reduced phosphorus and calcium balance in the same cohort [11]. Framing caution An absorption finding, not a deficiency state. No fluoride supplement is recommended. It matters mainly to clinicians managing fluoride therapy.

Limits on what this shows

• Null findings: None located for aluminum hydroxide and zinc in people with normal kidneys. No study measured zinc status over time.
• At-risk subgroups: Hemodialysis patients, who already have impaired zinc absorption and lower fasting plasma zinc [29].

Regulatory status

Zinc is not mentioned in the labels opened [1][2][3][4][5].

Population evidence

Abu-Hamdan 1986 [29]: oral zinc tolerance test (25 mg elemental zinc) in hemodialysis patients versus controls. Fasting plasma zinc was lower in patients (92 versus 108 micrograms/dL). Aluminum hydroxide reduced zinc absorption by 60 to 75% in patients (p less than 0.005); ferrous sulfate lowered the area under the curve by 28 to 40% in controls. Abstract level via OpenAlex reconstruction; group sizes and aluminum hydroxide dose not captured.

Mechanism

Luminal interference with absorption is the likely route; the abstract does not describe the mechanism.

Counter-evidence held on record

Counter-evidence and confounding Single study, acute co-ingestion rather than chronic therapy, uremic population. Ferrous sulfate produced a comparable reduction, so the effect may be non-specific competition when two minerals are swallowed together. A circulating consumer list also names zinc for Maalox and Mylanta [43] without a source. Framing caution Not a zinc deficiency claim. No zinc supplement is recommended; this supports separating doses, not adding zinc.

Limits on what this shows

• Null findings and tissue data: Clarkson's bone aluminum stayed within normal limits [19]. Saadeh's bone biopsy aluminum stain was negative after 13 years of use with normal kidneys [14], while Woodson found stainable aluminum on 27.6% of bone surface after 8 years with normal kidneys [17]. Sharp 1993 [28]: in 172 subjects, antacid consumption raised plasma aluminium but was not associated with significant changes in most bone-formation indices (antacid type not stated in the abstract; Tier C). Alfrey 1976 [22] reported tissue aluminum in dialysis patients (bone 98.5 versus 2.4 ppm; brain gray matter 25 ppm in encephalopathy) but the abstract does not name the source (Tier C for this drug). Kaehny 1977 [23], the classic antacid absorption study, was only partly readable (introduction), so its results are not used.
• At-risk subgroups: Chronic kidney disease, dialysis, children with kidney disease [20], critically ill patients with falling creatinine clearance (magaldrate data, Tier C) [27], people taking citrate with the antacid [24][25].

Regulatory status

21 CFR 331.80(a)(4): "Prolonged use of aluminum-containing antacids in patients with renal failure may result in or worsen dialysis osteomalacia." [4]. The three OTC labels say to ask a doctor before use with kidney disease [1][2][3]. The SmPC contraindicates use in renal insufficiency and notes accumulation, dementia and anemia risk [5]. PDR: avoid in renal failure [7].

Population evidence

Clarkson 1972 [19]: 8 chronic renal failure patients (creatinine clearance 4.9 to 22.0 mL/min) on aluminum hydroxide gel 75 to 150 mL daily for 20 to 32 days absorbed 100 to 568 mg aluminum per day; iliac bone aluminum rose in 2 or 3 patients but did not exceed normal values. Salusky 1991 [20]: randomized trial, 17 children and young adults on peritoneal dialysis (mean age 14.1), aluminum hydroxide 30 mg/kg/day versus calcium carbonate for about 13 months; more aluminum accumulation on aluminum hydroxide, and one patient developed aluminum-related bone disease. Tahiri 1983 [21]: 19 hemodialysis patients; plasma aluminum stayed near 81 micrograms/L before and after dialysate aluminum fell below 20 micrograms/L, and aluminum hydroxide dose correlated with reduced red-cell size, pointing to the oral drug as the dominant source. Healthy-volunteer absorption and the citrate effect are in [24][25].

Mechanism

Present: small gastrointestinal absorption (fraction about 10^-4, enhanced by citrate) [24][25] and renal clearance of the absorbed aluminum, which fails in renal impairment [4][5]. A review states OTC antacids are the main aluminium source for most people and that citrate-containing drinks enhance absorption [26] (Tier C narrative).

Counter-evidence held on record

Counter-evidence and confounding Dialysate and other sources add aluminum in dialysis patients; Tahiri tried to separate them but is a small abstract-level study [21]. Osteomalacia and encephalopathy are outcomes, not nutrient deficiencies (Hard Rule 2); the measured parameter is aluminum. Cross-reference: the sibling sucralfate dossier (b011) has an orange aluminum retention entry, but its cohorts studied sucralfate, not aluminum hydroxide, so by the cohort test none of its sources count here, and the two exposures add together only as a clinical matter. Why orange and not red: bone and neurologic outcomes in aluminum hydroxide users were seen in one trial patient [20], and Clarkson's bone aluminum did not exceed normal [19]. Framing caution This is an excess and retention risk. Supplementation of any nutrient is not the remedy; the hazard is cumulative aluminum exposure when excretion is impaired. Decisions about use in kidney disease belong to the prescriber.

Regulatory status

Major suspension: 200 mg aluminum hydroxide, 200 mg magnesium hydroxide and 20 mg simethicone per 5 mL; magnesium 83 mg per 5 mL; ask a doctor with kidney disease or a magnesium-restricted diet [1]. Magsil tablets carry the same warnings [2]. Gaviscon combines aluminum hydroxide with magnesium carbonate (magnesium 115 mg per tablespoon, regular strength) [3]. The SmPC states renal impairment raises plasma aluminium and magnesium [5].

Population evidence

No study measuring serum magnesium in users of aluminum and magnesium hydroxide products was opened. Label composition is the only evidence for this entry (Tier A for composition; no outcome data).

Mechanism

Present for magnesium: absorbed magnesium is renally cleared, and impaired kidney function is the label's stated concern [1][5]. Not a property of aluminum hydroxide.

Class cohort test

The sibling magnesium hydroxide dossier (b012) grades magnesium excess separately; its sources were not opened for this dossier and are not used. Case reports in the phosphate entry that used combination products [14][15][17] are confounded by the magnesium component.

Counter-evidence held on record

Counter-evidence and confounding Aluminum hydroxide alone also depletes phosphate in controlled experiments [10][11], so the phosphate entry does not depend on magnesium. Laxation by the magnesium component can offset the constipating effect of aluminum; the Gaviscon label warns of laxative effects [3]. Framing caution Excess and retention flag for people with kidney disease. Extra magnesium would be the hazard, not the remedy.

Limits on what this shows

• Null findings: None located for these three drugs.

Regulatory status

OTC labels: "Antacids may interact with certain prescription drugs" [1][2][3]. The SmPC lists tetracyclines, quinolones and ACE inhibitors as affected drugs [5].

Population evidence

Frost 1992 [32]: randomized crossover in healthy volunteers, 750 mg ciprofloxacin alone, with aluminum hydroxide tablets or with calcium carbonate; aluminum hydroxide reduced bioavailability to about 60% of control, calcium carbonate by 15%, with lower urinary recovery. Garty and Hurwitz 1980 [33]: 5 healthy volunteers, magnesium-aluminum hydroxide gel reduced tetracycline availability by about 90%; gastric pH itself did not alter absorption. Liel 1994 [34]: levothyroxine-treated patients, seven treatment periods of 2 to 4 weeks with aluminum hydroxide-containing medication, TSH 7.19 versus 2.62 mU/L (P = 0.012), plus in vitro adsorption of thyroxine by aluminum hydroxide. PDR separation intervals: tetracyclines 2 to 3 hours, quinolones 2 to 6 hours, thyroid hormones at least 4 hours [7].

Mechanism

Present: nonspecific adsorption or chelation in the gut lumen [34].

Counter-evidence held on record

Counter-evidence and confounding The evidence for the interaction itself is Tier A, but the entry is yellow because it is not a nutrient-status finding. Small samples; intervals vary by source and should be confirmed by a pharmacist. Calcium carbonate showed a smaller ciprofloxacin effect than aluminum hydroxide [32], so the sibling calcium carbonate dossier is not a substitute. Framing caution Separate the dosing times and recheck levothyroxine response; do not read this as a depletion.