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A Comprehensive Comparison of Phosphate Binders for Chronic Kidney Disease Management: An Evidence-Based ApproachÂ
Authos: Dr Sasan Dastaran
Hyperphosphatemia, a common complication in patients with chronic kidney disease (CKD), is associated with increased morbidity and mortality, including cardiovascular disease and bone disorders[1,2]. Phosphate binders play a crucial role in the management of hyperphosphatemia in CKD patients, particularly those on dialysis[3]. With a growing array of phosphate binders available, healthcare professionals must navigate the complexities of each agent to determine the most suitable option for their patients. In this article, we provide a detailed comparison of the most commonly prescribed phosphate binders, including sevelamer-based binders (Renvela and Renagel), calcium-based binders, lanthanum carbonate, and sucroferric oxyhydroxide, with a focus on their mechanisms of action, efficacy, side effects, and potential advantages and disadvantages, based on peer-reviewed evidence.
Sevelamer-based Phosphate Binders: Renvela and Renagel
Renvela (sevelamer carbonate) and Renagel (sevelamer hydrochloride) are non-calcium, non-metal-based phosphate binders with high efficacy in controlling hyperphosphatemia in CKD patients[4]. Both agents have the advantage of not increasing the risk of hypercalcemia and may even lower LDL cholesterol levels[4,5]. However, they may require a higher pill burden and are generally more expensive compared to calcium-based binders[4,6]. Common side effects include constipation, diarrhea, nausea, vomiting, abdominal pain, and flatulence[4].
Calcium-based Phosphate Binders
Calcium carbonate and calcium acetate are calcium-based phosphate binders that are effective and cost-efficient in treating hyperphosphatemia[4]. However, these agents may increase the risk of hypercalcemia and vascular calcification[4,7]. Common side effects include hypercalcemia, constipation, nausea, and vomiting[4].
Lanthanum Carbonate
Lanthanum carbonate is a metal-based phosphate binder that provides high efficacy without increasing the risk of hypercalcemia[4]. It has the added benefit of a lower pill burden compared to some other phosphate binders[4,8]. However, there is a risk of lanthanum accumulation, and it is generally more expensive than calcium-based binders[4,8]. Common side effects include constipation, diarrhea, nausea, vomiting, and abdominal pain[4].
Sucroferric Oxyhydroxide
Sucroferric oxyhydroxide is an iron-based phosphate binder that also provides high efficacy without increasing the risk of hypercalcemia[4]. It has a lower pill burden compared to some other phosphate binders[4,9]. However, there is a risk of iron overload, and it is generally more expensive than calcium-based binders[4,9]. Common side effects include diarrhea and dark-colored feces[4].
Conclusion
The selection of a phosphate binder should be based on the individual patient's needs, risks, and preferences, as well as the specific benefits and drawbacks of each phosphate binder. Sevelamer-based binders offer advantages in avoiding hypercalcemia but may require a higher pill burden and have a higher cost[4,6]. Calcium-based binders are cost-effective but may increase the risk of hypercalcemia and vascular calcification[4,7]. Lanthanum carbonate and sucroferric oxyhydroxide are alternative options with no hypercalcemia risk but may have higher costs and potential risks of metal accumulation or iron overload, respectively[4,8,9]. Ultimately, healthcare professionals must weigh the benefits, potential risks, and costs associated with each phosphate binder when making clinical decisions for their patients with chronic kidney disease. By considering individual patient factors and preferences, clinicians can optimize the management of hyperphosphatemia and improve overall patient outcomes.
References
Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis. 1998;31(4):607-617.
Isakova T, Nickolas TL, Denburg M, et al. KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. 2017;70(6):737-751.
Habbous S, Przech S, Acedillo R, et al. The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant. 2017;32(7):1117-1130.
Igarashi M, Shinki T, Sato T, et al. Cost-effectiveness of phosphate binders among patients with chronic kidney disease not yet on dialysis: a long way to go. Eur J Health Econ. 2021;22(6):881-891. doi:10.1007/s10198-021-01275-3
Tonelli M, Pannu N, Manns B. Oral phosphate binders in patients with kidney failure. N Engl J Med. 2010;362(14):1312-1324.
Komaba H, Fukagawa M. Phosphate-a poison for humans? Kidney Int. 2016;90(4):753-763.
Jamal SA, Vandermeer B, Raggi P, et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet. 2013;382(9900):1268-1277.
Evenepoel P, Selgas R, Caputo F, et al. Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients with end-stage renal disease. Nephrol Dial Transplant. 2019;34(5):798-809. doi:10.1093/ndt/gfy280
Floege J, Covic AC, Ketteler M, et al. A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients. Kidney Int. 2014;86(3):638-647.
Sevelamer Carbonate - Summary of Product Characteristics (SmPC) for Prescribers
NAME OF THE MEDICINAL PRODUCT
Sevelamer Carbonate
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains sevelamer carbonate equivalent to 800 mg sevelamer (as carbonate).
For the full list of excipients, see section 6.1.
PHARMACEUTICAL FORM
Tablet
White to off-white, oval-shaped, film-coated tablets.
CLINICAL PARTICULARS
4.1 Therapeutic indications
Sevelamer carbonate is indicated for the control of hyperphosphatemia in adult patients with chronic kidney disease (CKD) on dialysis.
4.2 Posology and method of administration
Posology
Adult patients:
Initial dose: 800 to 1600 mg with each meal, based on serum phosphorus levels.
Titrate in increments of 800 mg to achieve target serum phosphorus levels.
Pediatric patients:
Not recommended for use in children under 18 years of age.
Method of administration
Oral use.
Take with meals to optimize phosphate binding.
4.3 Contraindications
Hypersensitivity to sevelamer carbonate or to any of the excipients listed in section 6.1.
Bowel obstruction.
4.4 Special warnings and precautions for use
Monitor serum calcium, phosphate, and parathyroid hormone (PTH) levels regularly.
Caution in patients with dysphagia, swallowing disorders, or gastrointestinal motility disorders.
Sevelamer may reduce the bioavailability of some medications; separate administration by at least 1 hour.
4.5 Interaction with other medicinal products and other forms of interaction
Reduced bioavailability of ciprofloxacin, levothyroxine, and some other medications.
Separate administration of sevelamer and these medications by at least 1 hour.
4.6 Fertility, pregnancy, and lactation
Pregnancy: Limited data available; use only if clearly necessary.
Breastfeeding: Unknown if excreted in human milk; discontinue breastfeeding or sevelamer.
Fertility: No data available.
4.7 Effects on ability to drive and use machines
Sevelamer carbonate has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Common side effects:
Gastrointestinal disorders: constipation, diarrhea, dyspepsia, nausea, vomiting, abdominal pain, and flatulence.
Metabolism and nutrition disorders: hypophosphatemia, hypocalcemia.
Nervous system disorders: headache.
For a full list of side effects, see section 6.1.
4.9 Overdose
No specific antidote. Treatment is supportive and symptomatic.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs for treatment of hyperkalemia and hyperphosphatemia.
Mechanism of action: Sevelamer carbonate is a phosphate binder that lowers serum phosphate levels by binding to dietary phosphate in the gastrointestinal tract, reducing its absorption.
5.2 Pharmacokinetic properties
Sevelamer carbonate is not absorbed and has no systemic activity. It is eliminated primarily through feces.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose
Sodium starch glycolate
Colloidal anhydrous silica
Magnesium stearate
Hypromellose
Titanium dioxide
Macrogol
Talc
6.2 Incompatibilities
Not applicable
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