Improved phosphate binder approved for dialysis patients

It seems that there's always room for improvement when it comes to the treatment of hyperphosphatemia in dialysis patients. First came aluminum-containing phosphorus binders, which were found to be very effective in lowering phosphorous levels but caused multisystem toxicity and were, therefore, largely abandoned. Calcium-containing binders came next and were considered somewhat safer initially. "But these products were later found to accumulate and cause calcifications in multiple tissues, leading to increased mortality, particularly in the more advanced stage chronic kidney disease [CKD] patients on dialysis," noted A. Scott Mathis, Pharm.D., assistant director for clinical services and residency program director in the department of pharmacy at Saint Barnabas Medical Center in Livingston, N.J.

The introduction of non-calcium-, non-aluminum-containing phosphorus binders (e.g., Renagel/sevelamer HCl, Genzyme) was considered a significant improvement. The new binders were not systemically absorbed and provided phosphorus control without concerns of calcium or metal accumulation. The class made an even bigger stir in nephrology when a study published in Kidney International demonstrated that patients using sevelamer experienced a significantly lower rate of death (associated with control of coronary artery calcifications) compared with those treated with calcium-based phosphate binders.

Better safe than sorry

Similar to sevelamer HCl, sevelamer carbonate is indicated for control of serum phosphorus in CKD patients on dialysis, but the new agent is claimed to have a lower incidence of gastrointestinal (GI) adverse effects and a carbonate buffer. According to Mathis, the carbonate product's ability to maintain bicarbonate levels within the recommended KDOQI ranges is a significant advantage, since sevelamer HCl was shown in a recent study, published in the October issue of Artificial Organs, to cause small but persistent acid-base disturbances in hemodialysis patients. "Patients with CKD already have metabolic acidosis as a result of their disease," but sevelamer HCl was found to worsen the complication by reducing serum bicarbonate levels via HCl release in the gut, explained José Menoyo, M.D., senior medical director at Genzyme. "Because the carbonate product doesn't contribute to the chloride exchange, it has not been shown to worsen metabolic acidosis; in fact, it may actually improve it," he noted.

Since the carbonate and HCl products have the same active moiety, they share similar pharmacology, lowering serum phosphate concentrations by binding phosphate in the dietary tract and decreasing its absorption. "As a result of their action in the gut, both products have to be given with meals, three times daily" and adjusted at two-week intervals to obtain serum phosphorus targets, noted Mathis.

What to watch for

Despite its favorable GI tolerability claim, sevelamer is still contraindicated in patients with bowel obstruction and should be used with caution in those with dysphagia, swallowing disorders, severe GI motility disorders, or a history of major GI tract surgery.

Overall, treatment of hyperphosphatemia should focus on achieving and maintaining a serum phosphate concentration of less than 5.5 mg/dl through dietary restrictions, adequate or intensified dialysis, rational use of phosphate binders, and conservative use of oral or intravenous vitamin D or its analogs.

TIPS TO REMEMBER Renvela

THE AUTHOR is a writer and hospital pharmacist based in New Jersey.