Aluminum Hydroxide

Mechanism of Action

Aluminum hydroxide [Al(OH)3] dissociates into Al3+ and OH- in the stomach. The freed hydroxide groups then bind to free protons, ultimately producing water and insoluble aluminum salts, mostly Al(Cl)3, within the stomach. The proton binding serves to increase the overall pH of the stomach, i.e., less acidic, reducing the symptoms of indigestion. The produced aluminum salt primarily gets excreted in the feces, with less than 1% of the bioavailable aluminum absorbed within the GI tract.

Aluminum exists at a steady-state within the body, so the body manages transient increases in aluminum uptake from use as an antacid with an equivalent increase in urinary excretion of unmodified aluminum. However, the setpoint of that steady-state may become elevated with prolonged increased intake of aluminum, so aluminum hydroxide treatment should not be considered as a long-term solution for patients suffering from acid indigestion. Furthermore, patients with chronic kidney disease may not be able to excrete the increased aluminum and thus also should be carefully considered.

Topical aluminum hydroxide creates an acidic, hydrophilic layer over the area of irritation; this serves as a protective barrier to prevent infection and deter bacterial growth within the wound. 

As an adjuvant in vaccines, aluminum hydroxide is known to increase macrophage phagocytosis, possibly via the upregulation of the NLRP3-inflammasome, increasing uptake of the desired antigen. Additionally, it is known to facilitate what is known as the "repository effect," whereby the antigens aggregate on and around the molecule, which helps to prevent their degradation within the body.[6] 

Administration

Aluminum hydroxide when used as an antacid is to be delivered orally. Shake the aluminum hydroxide suspension well before use. It should be taken 5 to 6 times daily after meals and at bedtime, not to exceed 3.84 g per 24 hours. The patient should follow the dose with water intake.

Topical aluminum hydroxide should be applied to the desired area and left in place. Topical aluminum has minimal skin absorption, so topical treatment with aluminum hydroxide may require reapplication as necessary. 

The administration of aluminum hydroxide as an antacid should not be for prolonged management of patient symptoms. Similarly, aluminum hydroxide should not be administered to patients with renal impairment. In these instances, increased aluminum may precipitate more severe adverse effects or deplete the body's phosphate reserves.[4]

Adverse Effects

The primary side effects of aluminum hydroxide include hypomagnesemia, hypophosphatemia, constipation, and anemia.[5] Additionally, due to its ability to stimulate the immune system, there have been observed cases of persistent granulomas at the injection site of vaccines containing aluminum hydroxide.[7] Topical applications have not demonstrated any adverse effects, primarily because aluminum hydroxide does not get absorbed through the epidermis.[4] 

Contraindications

Aluminum hydroxide is contraindicated for patients with documented hypersensitivity to the drug. Prolonged administration should not be considered in a patient with renal impairment or a patient on dialysis, as impaired clearance of excess aluminum may precipitate the drug's adverse effects.[4] Due to aluminum hydroxide's ability to bind phosphate, it should not be administered in patients with severe diarrhea, as hypophosphatemia may become exacerbated. Additionally, the administration of aluminum hydroxide before the use of a fluoroquinolone such as ciprofloxacin has demonstrated a reduction in the bioavailability of the antimicrobial, reducing its efficacy. As such, it is not to be administered concurrently with these drugs. However, the patient can greatly mitigate this effect if the aluminum hydroxide is provided at least two hours after the antimicrobial.[8][9][10] Due to its nature as an alkalizing agent, it should also not be administered concurrently with drugs that depend upon acidic absorption, such as riociguat or raltegravir, as it will reduce the efficacy of these treatments.[11][12]

Monitoring

When administering aluminum hydroxide as an antacid, the patient should have monitoring of their calcium and phosphate plasma concentrations. Kidney function also requires monitoring, especially with prolonged use of aluminum hydroxide. 

Toxicity

Seizures, osteomalacia, and encephalopathy are well-documented toxic effects of aluminum hydroxide. Patients should be asked about any kidney issues before aluminum hydroxide administration, as these outcomes have strong correlations with aluminum hydroxide's use as a phosphate binder in patients on dialysis.[7] Most reports of encephalopathy and osteomalacia came from a period when water purification standards for dialysis were not as strong as they are now, likely confounding the relationship of oral aluminum to toxicity. Reversal of aluminum hydroxide toxicity occurs with the cessation of the drug. Topical aluminum hydroxide and aluminum hydroxide adjuvant vaccines have not shown to produce any toxic effects, primarily due to the small concentration associated with both applications. 

Enhancing Healthcare Team Outcomes

Managing the administration of aluminum hydroxide as an antacid to patients requires an interprofessional team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, social workers, and several physicians in different specialties. After the diagnosis of an illness treatable with aluminum hydroxide, such as heartburn, is made, care is necessary to ascertain if the patient possesses any risk factors or contraindications to aluminum hydroxide. 

Recommendations for Increasing Successful Outcomes of Antacid Aluminum Hydroxide Therapy

• Discontinue administration of aluminum hydroxide in patients with renal impairment. 
• Do not administer aluminum hydroxide concurrently with antimicrobials such as fluoroquinolones.
• Avoid the use of antacid treatment in patients taking medications that depend upon the acidic nature of the stomach for proper absorption.
• Prescribe aluminum hydroxide for temporary use rather than prolonged management
• Discontinue administration of aluminum hydroxide when used as an antacid if the patient develops severe diarrhea

The clinician and nurses should monitor the patient and report untoward findings to the team. Pharmacists can also counsel the patient regarding dosing and the proper application of topical dose forms. The pharmacist should also check for drug interactions. Complications or issues with therapy should be reported to the medical team. All practitioners should be aware of the potential problems of long-term use, and counsel and direct the patient accordingly, particularly in those with renal compromise. Interprofessional monitoring of patients taking aluminum hydroxide will lead to better outcomes. [Level 5]