Phosphate binders

Definition and Clinical Purpose

Phosphate binders are a class of non-absorbable oral medications that bind dietary phosphate in the gastrointestinal (GI) tract to prevent its absorption into the bloodstream. Their primary role is in the management of hyperphosphatemia—an abnormally high level of serum phosphate commonly observed in patients with chronic kidney disease (CKD), especially those on dialysis. Elevated serum phosphate contributes to secondary hyperparathyroidism, vascular calcification, renal osteodystrophy, and increased cardiovascular mortality.

Phosphate binders help maintain normal phosphate levels and correct calcium-phosphate product imbalances, forming a critical part of CKD-Mineral and Bone Disorder (CKD-MBD) management strategies.

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1. Classification of Phosphate Binders

Phosphate binders are classified by their chemical composition and metal content, particularly whether they contain calcium, aluminum, or are metal-free.

A. Calcium-Based Phosphate Binders

• Calcium carbonate

• Calcium acetate

B. Non-Calcium, Non-Metal Phosphate Binders

• Sevelamer hydrochloride

• Sevelamer carbonate

• Lanthanum carbonate

C. Iron-Based Phosphate Binders

• Sucroferric oxyhydroxide

• Ferric citrate

D. Aluminum-Based Phosphate Binders

• Aluminum hydroxide (rarely used due to toxicity)

E. Magnesium-Containing Phosphate Binders (Less common)

• Magnesium carbonate, magnesium hydroxide (occasionally in combination formulations)

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2. Mechanism of Action

Phosphate binders bind to dietary phosphate in the gut, forming insoluble phosphate complexes that are excreted in feces, thereby reducing phosphate absorption and lowering serum phosphate levels.

The binding depends on:

• pH of the GI tract (many bind better in acidic environments)

• Amount and type of phosphate consumed

• Dosing timing (must be taken with meals for optimal effect)

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3. Therapeutic Indications

Primary Indication

• Hyperphosphatemia in chronic kidney disease (CKD), particularly stages 4–5 and dialysis-dependent CKD (ESRD)

Other Potential Indications (Off-label/adjunct)

• Tumor lysis syndrome (phosphate elevation from cell lysis)

• Hyperphosphatemia due to hypoparathyroidism or vitamin D toxicity

• Management of secondary hyperparathyroidism (indirect)

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4. Generic Drug Names and Brand Examples

Generic Name	Brand Name(s)	Type
Calcium carbonate	Tums, Caltrate	Calcium-based
Calcium acetate	PhosLo, Eliphos	Calcium-based
Sevelamer hydrochloride	Renagel	Non-calcium, polymer-based
Sevelamer carbonate	Renvela	Non-calcium, polymer-based
Lanthanum carbonate	Fosrenol	Metal-based (non-Ca/Fe)
Sucroferric oxyhydroxide	Velphoro	Iron-based
Ferric citrate	Auryxia	Iron-based
Aluminum hydroxide	Alternagel, Amphojel	Aluminum-based (obsolete)

5. Pharmacokinetics

Agent	Absorption	Systemic Effects	Excretion
Calcium-based binders	Partial systemic Ca²⁺	Hypercalcemia risk	Fecal + renal
Sevelamer (carbonate/HCl)	Non-absorbed polymer	No systemic absorption	Fecal
Lanthanum carbonate	Minimal absorption	Trace systemic lanthanum	Fecal (primary)
Ferric citrate	Some Fe absorption	May increase iron stores	Fecal + limited renal
Sucroferric oxyhydroxide	Minimal Fe absorption	Lower iron absorption than ferric citrate	Fecal

6. Adverse Effects

Common Adverse Effects (All classes):

• Constipation

• Diarrhea

• Nausea

• Abdominal bloating or discomfort

• Flatulence

Specific Toxicities by Class:

Agent/Class	Specific Risks
Calcium-based	Hypercalcemia, vascular calcification, adynamic bone disease
Sevelamer	GI obstruction, acidosis (with HCl form), hypovitaminosis (binds fat-soluble vitamins)
Lanthanum carbonate	Nausea, myalgia, accumulation in bone and liver (theoretical), confusion (rare)
Ferric citrate	Iron overload, black stool, increased ferritin and TSAT
Sucroferric oxyhydroxide	Dark stools, diarrhea, minimal iron absorption
Aluminum hydroxide	Aluminum toxicity: encephalopathy, osteomalacia, anemia

7. Contraindications

• Bowel obstruction or ileus

• Hypophosphatemia

• Hypercalcemia (for calcium-based agents)

• Hemochromatosis or iron overload disorders (iron-based agents)

• Hypersensitivity to formulation components

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8. Precautions and Monitoring

Monitoring Parameter	Frequency
Serum phosphate	Every 1–4 weeks during titration, then monthly
Serum calcium	Monthly (more frequently with Ca-based agents)
Parathyroid hormone (PTH)	Every 3–6 months
Serum ferritin and TSAT	Quarterly if on iron-based binders
Aluminum levels	If on Al-hydroxide or long-term dialysis
Gastrointestinal tolerance	Continuously

9. Drug Interactions

Drug/Agent	Interaction
Tetracyclines, fluoroquinolones	Reduced bioavailability (chelation)
Levothyroxine	Binding and decreased efficacy
Iron supplements	Interaction with phosphate binders
Fat-soluble vitamins (A, D, E, K)	Binding by sevelamer; monitor levels
Oral bisphosphonates	Chelation and decreased absorption

Management:

• Separate administration by at least 1–2 hours before or after other oral medications

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10. Clinical Considerations and Guidelines

• KDIGO Guidelines (2020):

  • Target serum phosphate toward normal range

  • Avoid calcium overload; limit calcium-based binders if serum calcium is high or there’s arterial calcification

  • Consider non-calcium binders (e.g., sevelamer, lanthanum, iron-based) in dialysis patients

  • Adjust therapy based on PTH, calcium, and phosphate dynamics

• Calcium-based binders are cost-effective but carry calcification risk

• Sevelamer is preferred in patients with:

  • Hypercalcemia

  • Vascular calcification

  • High-normal calcium levels

• Iron-based binders are beneficial for patients with:

  • Concurrent anemia

  • Iron-deficiency or low ferritin

• Aluminum binders are obsolete due to toxicity risk; only used for short-term rescue

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11. Summary of Key Agents

Agent	Pros	Cons
Calcium acetate	Cost-effective, effective phosphate control	Hypercalcemia, vascular calcification
Sevelamer carbonate	No calcium load, lowers LDL cholesterol	Expensive, GI side effects
Lanthanum carbonate	Effective at low pill burden	Metal accumulation concern, taste issues
Ferric citrate	Dual benefit (binds phosphate, raises iron)	Risk of iron overload, GI effects
Sucroferric oxyhydroxide	Low systemic iron absorption	Dark stools, diarrhea
Aluminum hydroxide	Potent binder (short-term only)	Aluminum toxicity (bone, brain)