Pharmacology
When taken with meals, PhosLo (calcium acetate) combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in the feces. PhosLo is highly soluble at neutral pH, making the calcium readily available for binding to phosphate in the proximal small intestine. Calcium acetate is a more efficient phosphate binder than other calcium salts. When phosphate binding in the proximal small intestinal lumen occurs, the calcium available for absorption decreases, thus reducing the risk of hypercalcemia in these patients.
The absorption of phosphorus plays a critical role in the development of metabolic bone diseases in patients with chronic renal failure. The retention of phosphate plays a pivotal role in causing secondary hyperparathyroidism associated with osteodystrophy and soft tissue calcification. The majority of patients with advanced renal insufficiency (glomerular filtration rate less than 30 mL/min) exhibit phosphate retention with hyperphosphatemia.
The rate of removal of phosphate by dietary manipulation or by dialysis is insufficient to prevent hyperphosphatemia in most dialysis patients. Dialysis patients absorb 40% to 80% of dietary phosphorus. Therefore, the fraction of dietary phosphate absorbed from the diet needs to be reduced. Phosphate binders in most renal failure patients on maintenance dialysis are effective in accomplishing that.
Indications
PhosLo (calcium acetate) is indicated for the control of hyperphosphatemia in end stage renal failure.
Precautions
The safety and efficacy of PhosLo (calcium acetate) in children have not been established.
Excessive dosage of PhosLo (calcium acetate) could induce hypercalcemia; therefore, early in the treatment during dosage adjustment, serum calcium should be determined twice weekly, and monitored regularly thereafter. Should hypercalcemia develop, the dosage should be reduced or the treatment discontinued immediately depending on the severity of hypercalcemia. Calcium salts should not be given to patients on digitalis because hypercalcemia may precipitate cardiac arrhythmias. Therapy with phosphate binders should always be started at low doses and should not be increased without careful monitoring of serum calcium. An estimate of daily dietary calcium intake should be made initially and the intake adjusted as needed. Serum phosphorous should also be determined periodically.
The safety and efficacy of PhosLo (calcium acetate) in pregnant women has not been established; therefore, PhosLo (calcium acetate) should be prescribed during pregnancy only if the benefits outweigh potential risks. Animal reproduction studies have not been conducted with PhosLo (calcium acetate), nor is it known whether PhosLo (calcium acetate) can cause fetal harm when administered to pregnant women or whether it can affect reproductive capacity.
Supplied
Each white, round tablet, stamped “BRA200”, contains: 667 mg calcium acetate USP equal to 169 mg calcium. Nonmedicinal ingredients: polyethylene glycol 8000 NF. Bottles of 200. Tablets should be swallowed whole and not chewed. Store at controlled room temperature (15-30°C).
Contraindications
PhosLo (calcium acetate) is contraindicated in patients with hypercalcemia.
Warnings
PhosLo (calcium acetate) should not be given concurrently with calcium supplements because patients with end stage renal failure may develop hypercalcemia.
Progressive hypercalcemia due to overdose of calcium salts administered to patients with chronic renal impairment may be sufficiently severe to require emergency measures. Chronic hypercalcemia may lead to vascular calcification and other soft tissue calcifications. The serum calcium concentration should be monitored twice weekly during the early dose adjustment period and regularly thereafter. The serum calcium times phosphate (CaXP) product should not be allowed to exceed 5.33 mmol2/L2. Radiographic evaluation of the suspect anatomical region may be helpful in early detection of soft tissue calcification.
Adverse Effects
The most frequent adverse reaction to PhosLo (calcium acetate) was hypercalcemia, which occurred in 15% of the patients in clinical studies. Mild hypercalcemia (Ca >2.63 mmol/L) may be asymptomatic or manifest itself as constipation, anorexia, nausea and vomiting. More severe hypercalcemia (Ca >3 mmol/L) is associated with confusion, delirium, stupor and coma. The serum calcium concentration should be monitored, and the dose should be adjusted accordingly. Decreasing dialysate calcium concentration could reduce the incidence and severity of hypercalcemia induced by PhosLo (calcium acetate).
In clinical studies, 7% of patients experienced nausea (including vomiting) and gastrointestinal disturbance during PhosLo (calcium acetate) therapy. Frequently this was a consequence of hypercalcemia.
The long-term effect of PhosLo (calcium acetate) on the progression of vascular or soft tissue calcification has not been determined.
Overdose
Administration of PhosLo (calcium acetate) in excess of the appropriate daily dosage can cause severe hypercalcemia (see Adverse Effects).
Mild hypercalcemia is easily controlled by reducing the PhosLo (calcium acetate) dose or temporarily discontinuing therapy. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing PhosLo (calcium acetate) therapy.
Dosage
The recommended initial dose of PhosLo (calcium acetate) for the adult dialysis patient is 2 tablets with each meal. The dosage may be increased gradually to bring the serum phosphate value below 1.94 mmol/L, as long as hypercalcemia does not develop. Most patients require 3-4 tablets with each meal. Tablets should be swallowed whole and not chewed.
