Did You Know? Phosphate Binders

Serum Phosphate

Serum phosphate concentration is primarily determined by the ability of the kidneys to excrete dietary phosphate. In kidney disease, excretion can be impaired, leading to higher phosphate levels. Hyperphosphatemia has been associated with increased morbidity and mortality. Phosphate binders are used to treat hyperphosphatemia that stems from many different causes including hyperparathyroidism, bisphosphonates, vitamin D toxicity, and very commonly, kidney disease.¹ Acute hyperphosphatemia typically resolves in 6-12 hours if kidney function is sufficient, and the phosphate excretion can be increased with saline infusion.² Dietary phosphate restriction and phosphate binders are utilized to treat chronic hyperphosphatemia found in chronic kidney disease. In most patients, the goal is to maintain the serum phosphate concentration between 3.5 and 5.5 mg/dL. Phosphate binders work exactly as they sound- they attach to phosphate from food in the digestive tract, ultimately decreasing the amount of phosphate absorbed.³ For this reason, phosphate binders should ALWAYS BE TAKEN WITH MEALS to be effective. Phosphate binders are classified as calcium-containing or non-calcium

Phosphate binders are classified as calcium containing or non-calcium containing.  Typically, the non-calcium containing binders are preferred unless the serum calcium is low:

• Low calcium:  Use a calcium-based binder such as Phoslo (more $) or Tums (Less $).
• Normal-high: Use a non-calcium-based binder.  1^st line:  Sevelamer carbonate (Renvela) or Lanthanum carbonate (Fosrenol—chewable form).

Phosphate Binders⁴

	Calcium-Based	Calcium-Based	Calcium and Metal Free	Calcium and Metal Free	Metal-Based	Metal-Based
	Calcium Carbonate (Tums)	Calcium Acetate (PhosLo, Phoslyra)	Sevelamer Carbonate (Renvela)	Sevelamer Carbonate (Renvela)	Lanthanum Carbonate (Fosrenol)	Aluminum Hydroxide (Amphojel)
Content (mineral/metal/element)	Contains 40% elemental Ca2+ (200 mg elemental Ca2+ per 500 mg CaCO3)	Contains 25% elemental Ca2+ (169 mg elemental Ca2+ per 667 mg cap)	None	None	Contains 250, 500, 750, or 1000 mg elemental lanthanum per tablet	Contains 250, 500, 750, or 1000 mg elemental lanthanum per tablet
Forms	Liquid, tablet, chewable, capsule, gum	Capsule, tablet	Tablet, powder	Tablet	Tablet, chewable	Liquid Tablet Capsule
Dosing	OFF label use6 Not to exceed 2 grams/day	667mg/tab 2 tablets with each meal Inc. every 2-3 weeks up to 3-4 tablets with each meal7	Initial: (serum phosphorus) 5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times daily ≥7.5 mg/dL to <9 mg/dL: 1,200 to 1,600 mg 3 times daily ≥9 mg/dL: 1,600 mg 3 times daily Maintenance dose: adjustment based on serum phosphorous concentration (goal range of 3.5 to 5.5 mg/dL) Inc. dose by 400-800mg per meal at 2-week intervals8	Initial: (serum phosphorus) 5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times daily ≥7.5 mg/dL to <9 mg/dL: 1,200 to 1,600 mg 3 times daily ≥9 mg/dL: 1,600 mg 3 times daily Maintenance dose: adjustment based on serum phosphorous concentration (goal range of 3.5 to 5.5 mg/dL) Inc. dose by 400-800mg per meal at 2-week intervals8	Available 500mg, 750mg, 1000mg 1500mg divided with meals Inc. every 2-3 weeks up to 3000mg daily9	OFF label use10 For short-term use (≤4 weeks) in patients with severe hyperphosphatemia (eg, >7 mg/dL) despite other treatment
Side Effects	Headache, hypercalcemia, hypophosphatemia, abdominal pain, anorexia, constipation, flatulence	Hypercalcemia, diarrhea, nausea, vomiting	Metabolic acidosis, diarrhea, dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, peritonitis	Metabolic acidosis, diarrhea, dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, peritonitis	Diarrhea, nausea, vomiting, hypocalcemia, abdominal pain	Constipation, white speckled fecal, fecal impaction, nausea, stomach cramps, vomiting, hypomagnesemia
Advantages	Effective, inexpensive, readily available	Effective phosphate-binding, potentially for enhanced phosphate-binding capability over calcium carbonate, potentially less calcium absorption	Effective; no calcium/metal; not absorbed; assumed to have similar advantages as sevelamer-HCl; potentially improved acid-base balance	Effective; no calcium/metal; not absorbed; potential for reduced coronary/aortic calcification when compared with calcium-based binders in some studies; reduces plasma concentration of LDL-C	Effective; no calcium; chewable	Very effective phosphate-binding capacity; variety of forms
Disadvantages	Potential for hypercalcemia-associated risks including extraskeletal calcification and PTH suppression; GI side effects	Potential for hypercalcemia-associated risks including extraskeletal calcification and PTH suppression; more costly than calcium carbonate; GI side effects	Cost; may require calcium supplement in the presence of hypocalcemia; GI side effects	Cost; potential for decreased bicarbonate levels; may require calcium supplement in presence of hypocalcemia; GI side effects	Cost; potential for accumulation of lanthanum due to GI absorption, although long-term clinical consequences unknown; GI side effects, lots of interactions	Potential for aluminum toxicity; altered bone mineralization, dementia; GI side effects

References

1. “Overview of the causes and treatment of hyperphosphatemia”
2. “Overview of the causes and treatment of hyperphosphatemia”
3. Patient Guide
4. Licensed and Available Oral Phosphate Binders
5. CKD MBD Guidelines in English
6. “Calcium Carbonate” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
7. “Calcium Acetate” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
8. “Sevelamer” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
9. “Lanthanum” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
10. “Aluminum Hydroxide” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.

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