Alternagel

Since antacids are usually taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hard stools (constipation).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Applies to aluminum hydroxide: compounding gel, compounding powder, oral capsule, oral suspension, oral tablet

General

Although the majority of aluminum ingested is eliminated by the gastrointestinal tract, absorption of aluminum and increases in serum concentrations have been demonstrated. Accumulation of aluminum and resulting toxicity is confined to patients with renal dysfunction and impaired elimination of aluminum.[Ref]

Sources of aluminum in patients with renal failure have included water used for dialysate solutions, in addition to aluminum hydroxide. Adverse effects of aluminum accumulation in these patients has led to monitoring of water source aluminum content by dialysis units and periodic measurements of serum aluminum in patients undergoing chronic dialysis.

High aluminum concentrations in patients are generally also associated with high daily doses. One study suggested that increases in aluminum concentrations in uremic patients were most significant with daily doses greater than 3 grams of aluminum hydroxide. Age of the patient has also been directly correlated with aluminum concentrations with younger age groups perhaps demonstrating higher concentrations.

Concurrent administration of aluminum hydroxide with citrate containing products has been associated with unusually high serum concentrations of aluminum and, especially in cases of renal failure, severe toxicity. It was speculated that citrate increases the solubility and absorption of aluminum.

Aluminum concentrations during aluminum hydroxide therapy has also been correlated with body iron stores. One study demonstrated a negative correlation between serum aluminum concentrations and serum ferritin levels. It was postulated that high serum ferritin and high transferritin saturation might hamper gut absorption of aluminum.

During long-term use, aluminum has been shown to deposit in bone, joints, and the brain of patients who accumulate aluminum.[Ref]

Gastrointestinal

Gastrointestinal side effects have been reported the most frequently. These have included constipation and impaction. Generally, aluminum hydroxide (the active ingredient contained in Alternagel) is combined with another antacid so lower doses may be used to counterbalance the constipating effect.[Ref]

Metabolic

Metabolic side effects have included hypophosphatemia with the use of aluminum hydroxide (the active ingredient contained in Alternagel) In patients on long-term aluminum hydroxide therapy, especially in association with poor diets, hypophosphatemia may result in muscle weakness, rhabdomyolysis, hemolysis, and encephalopathy.[Ref]

Aluminum hydroxide complexes with phosphate in the gut to form insoluble aluminum phosphate, thus inhibiting the absorption of dietary phosphate. Aluminum hydroxide is commonly used in patients with renal dysfunction to regulate the accumulation of phosphate due to decreased elimination.

Hypophosphatemia is thought to stimulate the conversion of calcifediol (25-hydroxy vitamin D3) to calcitriol (1,25-dihydroxy vitamin D3), a potent stimulator of calcium and phosphorous intestinal absorption and osteoclastic resorption. Hypercalciuria is generally associated with hypophosphatemia.[Ref]

Musculoskeletal

Musculoskeletal adverse effects due to aluminum hydroxide (the active ingredient contained in Alternagel) commonly includes osteomalacia, which may occur by two different mechanisms. Osteomalacia may occur due to hypophosphatemia or due to aluminum accumulation in bone. Osteomalacia due to hypophosphatemia is often accompanied by malaise, bone pain, muscular weakness, and bone fractures. Osteomalacia due to aluminum deposition may present in a similar fashion and occurs predominantly in patients with chronic renal failure. Aluminum deposits are seen on bone biopsy.[Ref]

Aluminum hydroxide associated hypophosphatemia, if severe and chronic, results in decreased bone mineralization and potentially osteomalacia. Hypophosphatemia is also thought to stimulate the conversion of calcifediol (25-hydroxy vitamin D3) to calcitriol (1,25-dihydroxy vitamin D3), a potent stimulator of osteoclastic resorption, thus contributing to osteomalacia. These patients generally require phosphorus replacement therapy. Symptoms of osteomalacia may take several weeks to resolve.

Osteomalacia due to aluminum deposition in bone is generally only seen in patients with chronic renal failure. Bone formation slows in response to aluminum bone deposits. Aluminum may also deposit in joint tissue, resulting in arthropathy and hydrarthrosis.[Ref]

Nervous system

Nervous system side effects have included encephalopathy which has occasionally been reported in patients with renal failure on long-term therapy with aluminum hydroxide (the active ingredient contained in Alternagel) When available, basal and/or deferoxamine stimulated aluminum serum levels reveal high concentrations.[Ref]

Encephalopathy associated with aluminum accumulation is generally characterized by speech disorders, dysarthria, dyspraxia, dysphasia, tremor, myoclonus, seizures, coma, and death. EEG of patients with aluminum encephalopathy has shown paroxysmal slowing, and diffuse rhythmical bursts of delta activity.

The interval between commencement of aluminum hydroxide therapy and development of encephalopathy in eight reported cases ranged from three weeks to three months. In two of these patients, aluminum serum concentrations of 871 to 2267 mcg/L were reported. These patients were on concomitant sodium citrate therapy. Most chronic dialysis patients develop aluminum encephalopathy slowly over several years.[Ref]

Renal

Renal side effects have rarely included formation of renal calculi, most probably due to hypercalciuria, with the use of aluminum hydroxide (the active ingredient contained in Alternagel) [Ref]

Other

Antacids may interfere with drug therapies because of their effect on gastric pH, adsorption or binding to drugs, and changes in urinary pH.[Ref]

Some side effects of Alternagel may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

500 to 600 mg orally 4 to 6 times a day as needed, between meals and at bedtime.

500 to 1500 mg orally 4 to 6 times a day as needed, between meals and at bedtime.

Patients with renal failure may accumulate aluminum with chronic use. Serum aluminum levels should be monitored or another antacid chosen.